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Faculty Seminar Abstracts

DR. PHIL S. BARAN

The Scripps Research Institute

"Studies In Natural Product Synthesis"

ABSTRACT: There can be no more noble undertaking than the invention of medicines. Chemists that make up the engine of drug discovery are facing incredible pressure to do more with less in a highly restrictive and regulated process that is destined for failure more than 95% of the time. How can academic chemists working on natural products help these heroes of drug discovery – those in the pharmaceutical industry? With selected examples from our lab and others, this talk will focus on that question highlighting innovation in fundamental chemistry and new approaches to scalable chemical synthesis. The advantages of harnessing innate reactivity and embracing the logic of C–H functionalization will be demonstrated in this context as well as in the invention of reactions with broad utility in industrial settings.

Wednesday, May 13, 2015

DR. HELEN BLACKWELL

University of Wisconsin - Madison

"Synthetic Ligands for the Interception of Bacterial Communication"

ABSTRACT: We are developing chemical tools that attenuate cell-cell communication pathways in bacteria. Many bacteria communicate using small organic molecules and peptides to monitor their population densities in a process called “quorum sensing.” At high cell densities, bacteria use this signaling network to switch from an isolated, nomadic existence to that of a multicellular community. This lifestyle switch is significant; only in groups will pathogenic bacteria turn on virulence pathways and grow into drug-impervious communities called biofilms that are the basis of myriad chronic infections. In turn, certain symbiotic bacteria will only colonize their hosts and initiate beneficial behaviors at high population densities. Our research is broadly focused on the design, synthesis, and characterization of non-native ligands that can intercept quorum sensing and provide new insights into its role in host/microbe interactions. These molecules provide a novel approach to study quorum sensing with both spatial and temporal control in a range of settings. We have developed a series of efficient synthetic methods that provide us with straightforward access to these ligands. In addition, we have applied our quorum sensing antagonists and agonists in vitro and in vivo to investigate quorum sensing as an anti-infective target. This talk will introduce our research approach and highlight recent results.

Thursday, April 23, 2015

DR. NILAY HAZARI

Yale University

"Pincer Supported Transition Metal Complexes for the Hydrogenation of Carbon Dioxide and Dehydrogenation of Formic Acid"

ABSTRACT: Given the steady decline in the world’s fossil fuel reserves and the potential environmental consequences of continued fossil fuel use, there is considerable interest in the development of alternative carbon sources. Carbon dioxide is a particularly attractive feedstock owing to its high abundance, low cost and toxicity, and relative ease of transport. Formic acid is an especially promising target for the catalytic conversion of carbon dioxide. It is used as a preservative and insecticide and as an acid, reductant and carbon source in synthetic chemistry. In addition, formic acid could play a role as a material for chemical hydrogen storage. In this presentation the development of a series of pincer supported iridium and iron complexes for the catalytic hydrogenation of carbon dioxide to formic acid and the dehydrogenation of formic acid will be described.

Thursday, April 16, 2015

DR. CHAMPAK CHATTERJEE

University of Washington - Seattle

"Chemical Approaches To Study Ubiquitin-Like Proteins In Bacteria and Humans"

ABSTRACT: Not Available

Friday, April 10, 2015

DR. PEHR HARBURY

Stanford University

"TBA"

ABSTRACT:

Thursday, April 2, 2015

DR. KARL J. HALE

Queen's University - Belfast (NORTHERN IRELAND)

"Total Synthesis of the Antitumor Antibiotic, (-)-Echinosporin, and Some Recent Studies on the

Application of the O-Directed Free Radical Hydrostannation of Alkynes"

ABSTRACT:

Thursday, March 26, 2015

DR. MICHAEL A. BROOK

McMaster University

" “Structuring Interfaces with Structured Siloxanes”"

ABSTRACT: The silicone polymers that we contact every day are normally terrible mixtures of materials that vary in molecular weight, degree of functionality and network structure. This is because traditional routes to their preparation do not allow synthetic control. The Piers-Rubinsztajn (PR) reaction – the condensation of a hydrosilane with an alkoxysilane in the presence of B(C6F5)3 – provides a simple synthetic route to complex products,1 which allows us to test the proposal that challenges of precise synthesis are worth the effort. We will report the preparation of dendrons and dendrimers of up to 13000 MW using this process and examine the ability to control interfaces using PR-derived silicones.

Our group is also interested in direct application of silicones in microfluidic devices and in rendering silicones ‘more green’, both of which require the control of interfaces. Therefore, a second focus of the talk will be on wettable silicones,2 including those derived from boronic acids, and lignin-reinforced siloxane elasomters.3

" Bacteria, Cancer, and Addiction: Searching for Molecules that have Physiological Function"

ABSTRACT: Nature contains information to instruct scientists about what is possible. This can serve as an inspiration to probe the frontiers of biology and chemistry. At the same time, chemistry can contribute to our understanding of biology and also to our ability to manipulate complex systems for human health and welfare. The combination of the tools and principles of chemistry, together with the tools of modern biology, allows us to create complex synthetic and natural molecules, comprising processes with novel biological, chemical and physical properties. This lecture will illustrate the opportunities that lie at this interface of biological chemistry by describing a series of examples that we are actively working on in our laboratory. Including developing vaccines for treating heroin abuse, cell-to-cell communication within bacteria and how some of these quorum-sensing molecules display a symbiotic relationship to cancer immunosurveillance as it relates to TRAIL apoptotic pathway.

Thursday, March 19, 2015

DR. MATTHEW J. COOK

Queen's University - Belfast (NORTHERN IRELAND)

"Silicon, Spiroketals and Sigmatropic Rearrangements"

ABSTRACT: Silicon is the most abundant element in the earth’s crust however, it’s uses as a synthetic handle in organic chemistry has been limited due to the inert nature of the C-Si bond, with most applications being found in materials and polymer science. Recently, there has been a renaissance in organosilicon chemistry with new uses in synthetic and medicinal chemistry being reported.

We are developing new methods for the formation and uses of organic silicon compounds. The high stability of C-Si bonds make them an ideal functional group that can be carried through a synthetic sequence with little or no degradation followed activation under specific conditions to perform a key reaction. We have developed new hydrosilylation chemistry to install silicon groups in a rapid and stereodefined manner alongside showing the uses of the organosilanes in cross-coupling chemistry, oxidation reactions, sigmatropic rearrangements and as directing groups for allylic substitution reactions. The presented research will be our recent work in this area including the development and mechanistic investigation of cascade sigmatropic rearrangement and the applications of organosilanes to the selective and rapid formation of spiroketal moieties.

ABSTRACT: Numerous synthetic protocols have been devised which transform solution-dispersed templates into intricate plasmonic nanostructures. These investigations have led to breakthroughs in nanostructure shape engineering as well as an elucidation of the fundamental atomic-scale mechanisms. Adapting these protocols to substrate-immobilized templates presents a unique set of opportunities derived from the fact that templates can be defined at site-specific locations with a crystallographic orientation determined by a heteroepitaxial relationship with the underlying substrate. Through both the independent and synergetic use of galvanic replacement reactions and seed mediated heterogeneous nucleation agents we, for the first time, demonstrate the synthesis of periodic arrays of substrate-based plasmonic nanostructures which exhibit (i) symmetry breaking characteristics, (ii) shell, core-shell and nanocage morphologies and (iii) tunable bimetallic and multimetallic alloy compositions. A mechanistic understanding of these substrate-based reactions will be presented with a focus on (i) the dramatic effect of template surface passivation, (ii) facet dependent hollowing, (iii) the role of defect transfer during shell growth and (iv) the role that substrate-template heteroepitaxy plays in orienting the end product. These studies aim to establish the mechanistic framework and synthetic protocols required to place shape-engineered substrate-based plasmonic nanostructures at site-specific locations, a capability which will enable the fabrication of advanced sensing devices with plasmonic elements as the active component.

Thursday, March 5, 2015

DR. MARK W. GRINSTAFF

Boston University

"Poly-amido-saccharides as New Carbohydrate Polymers and Biomaterials"

ABSTRACT: The chemical synthesis of high molecular weight polysaccharides is challenging for polymer chemists and new, robust approaches are needed. Introducing an amide linkage between monosaccharide repeat units instead of an ether linkage is a strategy that could allow the molecular-level control available via organic synthesis while preserving some of the unique properties of natural polysaccharides. The synthesis and characterization of chiral, controlled molecular weight poly-amido-saccharides via the anionic ring opening polymerization of a beta-lactam sugar monomer will be presented. In addition to polymer characterization data, bioactivity studies and potential biomaterials applications of poly-amido-saccharides will be addressed.

Thursday, February 26, 2015

DR. MARK R. BISCOE

The City College of New York

"Rethinking Asymmetric Synthesis: The Development of General Metal-Catalyzed Cross-Coupling Reactions That Enable the Use of Optically Active Nucleophiles"

ABSTRACT: The development of transition metal-catalyzed cross-coupling reactions has greatly influenced the manner in which the synthesis of complex organic molecules is approached. A wide variety of methods are now available for the formation of C(sp2)–C(sp2) bonds, and more recent work has focused on the use of C(sp3) electrophiles and nucleophiles. The use of secondary and tertiary alkyl nucleophiles in cross-coupling reactions remains an outstanding challenge because of the propensity of these alkyl groups to isomerize under the reaction conditions. Our research group seeks to develop efficient, general methods to use secondary and tertiary organometallic nucleophiles in cross- coupling reactions. Further, we seek to extend this chemistry to the use of configurationally stable, optically active nucleophiles in stereospecific cross- coupling reactions. Such processes would enable the rapid generation of libraries of non-racemic drug candidates from a single optically active precursor. In this seminar, progress towards these goals will be presented.

ABSTRACT: Peptide nucleic acid (PNA) is a synthetic analogue of DNA that contains the same nucleobases as DNA and forms duplexes based upon Watson-Crick rules of hybridization but has a pseudo-peptide backbone. Substitution of PNA nucleobases with ligands can be used to confer metal affinity to PNA and represents a method for controlled metal incorporation in PNA structures. This method has been used already for incorporation of metal ions in DNA but PNA, with its neutral, achiral, and non-natural backbone, presents advantages over DNA when used to synthesize functional, hybrid inorganic-nucleic acid structures for applications in nano- or bio-technology.

This presentation will describe the interplay between nucleobase hybridization and metal-ligand coordination on the properties of metal-containing PNA duplexes, which has been studied by a combination of spectroscopic and structural methods. The implications of these findings for the use of the metal-containing PNAs in nanotechnology applications will be discussed also.

Thursday, January 29, 2015

DR. JOEL ROSENTHAL

University of Delaware

"Developmjent of New Catalyst Materials and Light Harvesting Assemblies for the Conversion of Carbon to Solar Fuels"

ABSTRACT: Current concerns over greenhouse gas (GHG) emissions and climate change highlight the need for renewable energy generation on a global scale. In the future, the sun will have a predominate role in sustainable energy production, however, cost-­‐effective energy storage is needed for sunlight to be harnessed as humanity's primary energy source. An intriguing strategy in this regard is the electrochemical reduction of CO2 to CO, which generates an energy rich commodity chemical that can be coupled to liquid fuel production, however there are few affordable platforms that can efficiently promote this transformation. In response to this need, we have developed several inexpensive cathode materials for CO2 reduction that can be prepared using a combination of electrodeposition techniques. These catalyst platforms can be used in conjunction with ionic liquids and other weak organic acids to effect the electrocatalytic conversion of CO2 to CO with high current densities at low overpotentials. The systems we will describe are selective for production of CO, and display activity levels that have historically only been observed using precious metal catalysts. Moreover, since coupling robust electrocatalysts for CO2 reduction with renewable sources of electricity is an attractive route to sustainable fuel production, we have married our catalyst systems with photoelectrochemical (PEC) assemblies that facilitate the production of solar fuels. We will show that interfacing a triple-­‐junction amorphous silicon photovoltaic with the inexpensive cathode materials developed in our lab, enables the storage of solar energy with good efficiency via the energetically uphill conversion of CO2 to CO.

In addition to developing new inexpensive platforms for CO2 reduction and solar fuel production, we have also worked to elucidate the molecular design principles that are attendant to the energy efficient activation of CO2 activation. Interrogation of the pathway by which our catalyst systems activate CO2 using a suite of electrochemical and surface analysis techniques, has revealed the primary factors that drive fuel generation. Implications for the future development of efficient architectures that can promote CO2 reduction with high selectivity and efficiency will be discussed.

Thursday, December 4, 2014

DR. GERRY WRIGHT

McMaster University (CANADA)

"Revisiting Natural Products To Address the Antibiotics Crisis"

ABSTRACT: Natural products from microbes have historically been the source of most of our antimicrobial agents. However, for the past three decades, the pharmaceutical sector has looked to synthetic compounds instead forantimicrobialleads as the natural product well appeared to have been exhausted. The lack of success in mining synthetic compounds for leads for new antimicrobial agents has contributed to the flight of the pharmaceutical sector from antibiotic discovery leaving an innovation gap at a critical time when antibiotics are increasingly needed as multi drug resistance in many microbial pathogens is on the rise.To address the antibiotic crisis, we are using resistance itself as a target for drug discovery. Our efforts in these areas are focused on a re-exploration of the sources of first generation antibiotics, the soil microbes (bacteria and fungi) that have proven such a rich source of drugs. We are identifying molecules produced by environmental microbes that directly and indirectly block resistance. Such molecules, called antibiotic adjuvants, are deployed in combination with first generation antibiotics to overcome resistance and rescue the activity of our legacy drugs. This strategy is enabling us to identify new compounds that have the potential to extend the lifetimes of our current antibiotic arsenal.

Thursday, November 20, 2014

DR. BENJAMIN GILBERT

Lawrence Berkeley National Laboratory

"Geochemical Reaction Intermediates In Metal Redox Cycling"

ABSTRACT:

Redox-active metals in the environment, including iron and manganese, undergo cycles of oxidation state change driven by photochemical, geochemical and biological processes. In low-temperature aqueous settings, including surface waters, soils and sediments, metal redox cycling frequently involves the formation or dissolution of minerals, including nanoparticles. Such redox reactions control the speciation and mobility of these metals as well as contaminants and nutrients that can sorb to the surfaces of mineral precipitates or participate in electron-transfer processes. A robust understanding of metal redox cycling is required to anticipate how near-surface settings evolve in response to environmental change.

Metal redox reactions proceed through a combination of chemical steps that can include electron and proton transfer, the breaking or formation of bonds, and mineral phase transformation. The rate and yield of the overall reaction depends upon the nature and lifetime of reaction intermediates, information that is typically not accessible by conventional kinetics studies. For example, it has been proposed that structural iron(II) sites are key intermediates in (photo)reduction reactions of iron(III) oxides, but direct observation of such species has been impossible until very recently. This presentation will give an introduction to time-resolved experimental methods that provide direct characterization of geochemical reaction intermediates. We are using these methods to identify crystal and solution chemical controls on the rates and yields of environmental metal cycling.

Thursday, November 13, 2014

DR. S. deBRION

"THz Magneto Electric Excitations In Multiferroic Compounds"

ABSTRACT: The electric-field control of spins and the converse magnetic-field control of electric dipoles inspire a number of hybrid technologies and motivates fundamental research on multiferroics and magnetoelectric materials. These magnetoelectric couplings produce striking phenomena both at the static and at the dynamical level. A prominent example is the electric-charge dressing of magnons, resulting in the so-called electromagnons, that has been demonstrated experimentally in multiferroics . This dressing enables the electric-field control of spin-waves with potential applications in photonics and magnonics. Several microscopic mechanisms for these ME coupling have been proposed, that vary with the investigated material, and even within the same compound. Here we report on new mechanisms for ME excitations that we have evidenced combining THz/FIR spectroscopies with inelastic neutron measurements.

Wednesday, November 12, 2014

DR. STEVEN E. WHEELER

Texas A & M University

"Toward A More Complete Understanding of Non-Covalent Interactions and the Computational Design of Organocatalysis"

ABSTRACT:

Non-covalent interactions involving aromatic rings (π-stacking interactions, cation-π interactions, anion-π interactions, etc) are central to many areas of modern chemistry research. I will describe the progress we have made understanding the nature of these non-covalent interactions and how their strength is impacted by substituents and heteroatoms. These non-covalent interactions also play key roles in many organocatalytic reactions. I will describe our recent efforts to quantify the role of anion-π interactions in “anion-π catalysis”, and will also present new catalysts that successfully exploit anion-π interactions to lower the activation energy for the Kemp elimination of 5-nitrobenzisoxazole. Finally, I will describe our progress towards the rational, computational design of organocatalysts for asymmetric propargylations of aromatic aldehydes. In particular, I will demonstrate results obtained using our computational toolkit AARON (Automated Alkylation Reaction Optimizer for N-oxides), which enables the automated computational screening of bidentate Lewis base catalysts for alkylation reactions.

ABSTRACT: Quantum confined semiconductor nanocrystals have emerged as a new class of light harvesting and charge separation materials in photovoltaic and photocatalytic devices. Compared with single component quantum dots (or “artificial atoms”), semiconductor nanoheterostructures (or “artificial molecules”), consisting of two or more component materials, offer additional opportunities to control charge separation properties by tailoring their compositions and dimensions through wavefunction engineering. With (quasi-) type II band alignment, both fast forward charge transfer (charge separation and hole filling) and slow backward recombination (charge recombination and exciton-exciton annihilation) can be achieved, enhancing the charge separation efficiency. Near-unity quantum yield of redox mediator (methylviologen radical) generation can be obtained in asymmetric CdSe/CdS dot-in-rod nano-heterostructures. When coupled with catalysts (Pt), these nanorods led to a much higher solar-driven hydrogen generation efficiency compared to molecular dyes and other nanocrystals. Quantum dots can also form “Artificial solid” electrodes with high carrier mobility and strong quantum confinement effect, enabling their integration into photoelectrochemical water splitting devices. In this talk, we will discuss how the fundamental charge transfer dynamics in these nanostructures can be directly probed by time-resolved spectroscopy and used to guide the design and optimization of nanoheterostructures for efficient light-driven H2 generation. (Relevant publications: Acc. Chem. Res. 2013, 46, 1270-1279, JACS (2014), DOI: 10.1021/ja5023893. Nano Lett. (2013), 13(11), 5255-5263, (2014), 14, 1263-1269)

Thursday, October 23, 2014

DR. WILLIAM DeGRADO

University of California - San Francisco

"Analysis and Design of Proton Transporters"

ABSTRACT: The mechanism of proton transport through membrane proteins is of general interest to multiple areas of biology. Using a variety of spectroscopic, crystallographic, and computational methods, we have investigated the mechanism by which protons are conducted through the M2 proton channel from influenza A virus, and used this information to design new anti-influenza drugs that target highly drug-resistant forms of the virus. A second topic of the talk will focus on the use of de novo protein design to test the mechanism by which a class of transporters uses proton gradients to drive the conduction of molecules into or out of cells. Transporters have been hypothesized to arise by physical association or gene duplication of primordial units, leading to an assembly with “frustrated symmetry” that rocks between two states with the substrate-binding site alternately accessing each side of the membrane. Rocker, a minimalist Zn2+/proton antiporter was designed to test these principles, although it bears no sequence similarity to any known natural protein. Structural, dynamic and functional studies indicate that Rocker is a primordial transporter, which recapitulates many of the properties of this class of proteins. These studies also demonstrate the feasibility of using de novo design to design membrane proteins with complex dynamic and functional properties.

ABSTRACT: Several new methods for introducing heteroatoms into hydrocarbon frameworks using transition metal catalysis will be discussed. This will include efforts towards developing palladium-catalyzed silyl-Heck reactions for preparing unsaturated organosilanes from simple alkenes. In addition, new alkylation strategies for nitroalkanes and primary amides using copper catalysis will be described.

ABSTRACT: Posttranslational modification of proteins by ubiquitin (Ub) and ubiquitin-like proteins (Ubls) represents a crucial way of regulating cellular functions. New pathways regulated by ubiquitin and Ubl are being discovered at a fast pace, virtually in every important aspect of biology. Enzymatic ubiquitination usually requires multiple enzymes and faces the problem of poor yield and homogeneity. Chemical ubiquitination circumvents the requirement of the ubiquitin enzyme cascade and can be readily generalized for modifying different target proteins. We have developed chemical approaches for efficient mono- and poly-ubiquitination of proteins. Using the chemically ubiquitinated proliferating cell nuclear antigen (PCNA) we uncovered new insights into the regulation of eukaryotic DNA damage response. Deubiquitinases (DUBs) erase the ubiquitin code and are known to be important for a number of cellular processes and linked to many human diseases. We have recently developed DUB probes that allowed the interrogation of DUB ubiquitin linkage specificity and small molecule allosteric inhibitors towards human USP1/UAF1. The USP1/UAF1 inhibitor disrupts cellular DNA damage tolerance and repair pathways, i.e. Fanconi Anemia (FA) and DNA translesion synthesis (TLS). The USP1/UAF1 inhibitor also acts synergistically in potentiating non-small cell lung cancer (NSCLC) cells to cisplatin. The therapeutic potential of the inhibitor is being evaluated in disease models for treating cancer.

Thursday, October 2, 2014

DR. MARK A. JOHNSON

Yale University

"Integrating Cryogenic Ion Chemistry, Laser Spectroscopy and Mass Spectrometry Into A Single Instrument:

A Powerful New Way To Trap and Probe Transients In Chemical Reactions"

ABSTRACT: Cryogenic processing of mass-selected ions provides a general means with which to trap labile reaction intermediates. This is accomplished by first cooling the ions close to 10K and condensing onto them dozens of weakly bound, chemically inert small molecules or rare gas atoms. This assembly can then be used as a medium in which to quench reactive encounters by rapid evaporation of the adducts, as well as provide a universal means for acquiring highly resolved vibrational spectra of the embedded species by photoinduced mass-loss. The capabilities of this approach will be illustrated by presenting recent applications to peptides, microhydrated ions, and biomimetic catalysts.

ABSTRACT: AMO studies have shaped our understanding of electron correlation, single photon multiple ionization, Auger processes, and photo-dissociation dynamics, all processes that are fundamentally important and occur in more complex chemical and biological systems. The commonality of the broad spectrum of the portfolio of photon and electron scattering studies is the use of targets that are in their ground state. In the case of photon-driven chemistry, the unprecedented ability of having two or three tailored extreme-ultraviolet photons opens up a large spectrum of possibilities that will help shed light on some of the most basic electronic and molecular processes that take place in excited states and drive photochemistry. In electron-driven chemistry, dissociation dynamics in the excited-state is initiated by a resonant capture of a low-energy electron (0-10 eV) to an unoccupied orbital forming a shape or Feshbach resonance. In both these cases the resulting electronic excited state is far from equilibrium and short lived. Electronic processes such as auto-ionization or radiative decay tend to quench these neutral and ionic excited states on very short timescale (femtoseconds). Consequently, Nuclear dynamics, isomerization and redistribution of energy between the various nuclear degrees of freedom, have to be very fast to compete with these processes. Nuclear and electronic degrees of freedom tend to couple and interesting non-adiabatic phenomena are known to arise. A particularly important example is conical intersections. Because of the breakdown of the Born-Oppenheimer approximation, conical intersections provide pathways for ultrafast interstate crossing, typically on the femtosecond time scale. Conical intersections can be found already in low-lying states of very simple molecules such as water, ethylene, carbon dioxide, or somewhat more complex systems such as formic acid or uracil. My talk will focus on the progress made using ultrafast lasers as well as low-energy electron sources coupled with momentum imaging.

Thursday, September 18, 2014

DR. HARRY GRAY

California Institute of Technology

"The 21st Century Solar Army"

ABSTRACT: The sun is a boundless source of clean energy, but it goes down every night. We and many others are trying to design solar-driven molecular machines that could be used on a global scale to store solar energy by splitting water into its elemental components, hydrogen and oxygen. Hydrogen is a clean fuel that could be used directly or combined with carbon dioxide to produce methanol, a liquid fuel. We are investigating the structures and mechanisms of hydrogen evolving catalysts made from Earth abundant elements such as cobalt, iron, nickel, and molybdenum. We also are employing pulsed laser ablation for synthesis of metal-oxide nanoparticles that will be deployed as catalysts on photoanodes such as tungsten oxide. To aid our research, we have recruited hundreds of students to join a Solar Army whose mission is the discovery of mixed-metal oxides for testing the photoanodes of our solar water splitters.

ABSTRACT: The alpha-imino anion (2-azaallyl anion) is a versatile synthon for the construction of nitrogen-containing organic frameworks including natural product architectures. Access to semi-stabilized a-imino anion intermediates typically requires strongly basic pyrophoric reagents and cryogenic conditions, thus limiting the range of tolerated functional groups. The presented research will focus on the palladium-catalyzed decarboxylative allylation and benzylation of 2,2-diphenylglycinate iminoesters as a mild and relatively neutral strategy for the generation and derivatization of a-imino anions. Mechanistic studies, highly enantioselective reaction conditions, and application to bioactive peptidomemtics and alkaloids will be addressed.

ABSTRACT: Oxygen reduction reaction (ORR) is one of the most important processes in fuel cells as well as in biological system. Pt based electrocatalyst is most efficient for ORR with low overpotential. However, due to high cost, less abundance, poor stability in electrochemical environment, and still sluggish kinetics of Pt based catalysts, there are worldwide research efforts to find non-precious metal catalysts. N- and B-doped carbon materials have been demonstrated to be effective metal free ORR catalysts and one may expect the increase of ORR activity by consecutive substitution of carbon atoms in graphene by B and N atoms. In an extreme case, if all carbon atoms in graphene are substituted by B and N atoms, hexagonal boron nitride (h-BN) monolayer, which has geometric structure similar to the graphene, is obtained. Although BN is an insulator with a wide band gap (5.8eV), our recent theoretical studies showed that the band gap of h-BN monolayer can be considerably reduced by B- and N- vacancy and impurity defects as well as by interaction with various substrates and BN on appropriate substrates can be used as an ORR catalyst.1-3 In the present study, ORR activity of BN nanosheets (BNNS) on Au(111) is predicted theoretically and proved experimentally.4,5

DFT calculations for BN/Au(111) show a slight protrusion of the unoccupied BN states towards the Fermi level due to the interaction between BN and Au(111) and presence of a metastable highly activated configuration of O2 on h-BN/Au(111) with the binding energy of -0.05 eV and stable configurations of O2 adsorbed at the edge of the BN islands on Au(111) surface, showing the possible ORR activity of BN/Au(111).

Electrocatalytic activities of various types of h-BN, i.e., spin coated BN nanotube (BNNT) and BN nanosheet (BNNS) and sputter deposited BN, on Au electrodes as well as those of BNNS modified glassy carbon (GC) and Pt electrodes for oxygen reduction reaction (ORR) were examined in O2 saturated 0.5M H2SO4 solution based on the theoretical prediction. The overpotential for ORR at Au electrode was reduced by ca. 100, ca. 270, and ca.150 mV by spin coating of the dispersion of BNNT and liquid exfoliated BNNS, and sputter deposition of BN, respectively, proving the theoretical prediction. The reason why the highest activity was obtained by the BNNS modification is attributed to the presence of B-and/or N-edge structures. The kinetic parameters were determined and the difference in the Tafel slope at the BNNS modified Au electrode was noticed.

While the BNNS modification was very effective to improve ORR activity at Au electrode, it has no and negative effects at GC and Pt electrodes, respectively, confirming the important role of BN-substrate interaction for ORR activity enhancement.

“The Mechanism of Solar Water Oxidation: The Role of Proton-coupled Electron Transfer Reactions in Photosystem II”

ABSTRACT: The solar water-splitting protein complex, photosystem II (PSII), catalyzes one of the most energetically demanding reactions in Nature by using light energy to drive water oxidation. The four-electron water oxidation reaction occurs at the tetranuclear manganese-calcium-oxo (Mn4Ca-oxo) cluster that is present in the oxygen-evolving complex of PSII. Proton-coupled electron transfer (PCET) reactions, which are exquisitely tuned by smart protein matrix effects, are central to the water-oxidation chemistry of PSII. However, the details of PCET processes are not yet understood because of the inability of conventional methods to probe these processes. A major challenge is to develop methods to directly investigate the mechanism of PCET reactions. I will describe ongoing efforts in our laboratory to understand the tuning and regulation of the PCET reactions of PSII. We are developing two-dimensional (2D) hyperfine sublevel correlation spectroscopy methods that provide direct ‘snapshots’ of the photochemical intermediates of the Mn4Ca-oxo,1-4 tyrosine5-6 and quinone7-8 cofactors of PSII.

*This project is supported by the Photosynthetic Systems Program, Office of Basic Energy Sciences, United States Department of Energy (DE-FG02-07ER15903).

ABSTRACT: Natural products and their derivatives have long been used as medicinal agents, and they still make up a significant fraction of clinically approved drugs. Recently, the trend in drug discovery is toward compounds that are much simpler than natural products, typically synthetic compounds that have few sp3-hybridized carbons and few stereogenic centers. While such compounds have value for certain types of targets (e.g., active sites of enzymes that accommodate flat substrates), there are certain targets and disease areas that are best modulated with complex molecules. This lecture will describe our discovery of a “simple” compound that is advancing rapidly toward human trials for the treatment of cancer, and the use of natural products as the starting point for the synthesis of collections of complex and diverse compounds. The compounds created through this latter effort have value in many different disease areas.

Thursday, May 1, 2014

DR. JUNRONG ZHENG

Rice University

“Molecular Vibrations: A Structural Tool”

ABSTRACT: Methodology of ultrafast nonlinear vibrational spectroscopy in determining three dimensional molecular conformations in liquids, solids and on nanomaterials surfaces and transient (<1ns) short-range (<1nm) molecular interactions in liquids is introduced. The method directly measures the cross angles among vibrations that cover the entire molecular space. The vibrational angles are then translated into cross angles among chemical bonds. The 3D molecular conformations are constructed by these bond angles. The distance between two vibrations is determined by vibrational energy transfers. The measurements on the formations of ion pairs and clusters in strong electrolyte aqueous solutions are used to demonstrate the principle. Systematic studies also suggest new views on intermolecular vibrational energy transfers in condensed phases.

ABSTRACT: Mass spectrometry is often the method of choice for solving difficult problems in chemical analysis, owing to its high sensitivity, specificity, and applicability to complex mixtures. Most applications of mass spectrometry involve identification of bond connectivity, whether through fingerprinting of small molecules for molecular identification or determining structures of proteins and protein modifications via fragmentation methods. New and emerging methods make possible detailed structural characterization of noncovalent interactions. Information about protein conformation, dynamics, and macromolecular assemblies can be obtained by combining both solution-phase methods with mass spectrometry analysis. The role of water on ion structure and stability can be examined using both electrochemical and photochemical methods, and new information about how ions affect the intermolecular interactions of water itself can be obtained. These gas-phase measurements can provide a bridge to understanding ion structure and solvation in the condensed phase.

Thursday, April 17, 2014

DR. JEREMY A. MAY

University of Houston

“Synthetic Discoveries from Polycyclic Natural Products”

ABSTRACT: The genus Flindersia produces bis-indole alkaloids that have demonstrated antimalarial activity. At least one of these natural products is toxic to Plasmodia falciparum via a novelmechanism of action. Work toward the biomimetic and enantioselective total synthesis of these alkaloids has led to discoveries in these natural products’ biosynthesis as well asmethods for stereoselective catalysis to generate chiral heterocycles. Specifically, acidic conditions that provide control over structural isomer formation have been defined for thebiomimetic synthesis of the alkaloids. To facilitate enantioselective synthesis of the compounds, an enantioselective organocatalytic addition of boronate nucleophiles to β-heterocycleappended enones was developed. This transformation has proven general for the synthesis of alpha-chiral heterocycles.
Another line of research targets the synthesis of biologically-active bridged polycyclic terpenoid natural products via a carbene-initiated cascade sequence. A terminal C-H bondinsertion allows for the controlled formation of a variety of bridged ring geometries. This strategy allows for the rapid synthesis of the target molecules' cores with substantial flexibility.

ABSTRACT: Assembling semiconductor nanostructures on electrode surfaces in a controlled fashion is an attractive approach for designing next generation solar cells. In recent years, quantum dot solar cells (QDSC) and Organometal Halide Perovskites have emerged as the potential contenders for making transformative changes. By assembling different size CdSe quantum dots on mesoscopic TiO2 films either by direct adsorption or with the aid of molecular linkers we have designed quantum dot solar cells. Upon bandgap excitation, CdSe quantum dots inject electrons into TiO2 thus enabling the generation of photocurrent in a photoelectrochemical solar cell. Compared to the electron injection rate, the hole transfer rate across the semiconductor interface remains a bottleneck in achieving photoconversion efficiency greater than 6%. Composition controlled tuning of bandgap has enabled us to design tandem layers of CdSeS QDs of varying bandgap within the photoactive anode of Quantum Dot Solar Cell (QDSC). Organometal halide perovskites have now emerged as new and promising candidates for developing low cost thin film solar cells. Recent advances that led to the development of high efficiency perovskite solar cells will be described.

ABSTRACT: Eukaryotes have been sharing the planet with bacteria throughout their evolutionary history, and this long association has led to highly varied interactions that are largely modulated by small molecules. Today’s lecture focuses on what can be learned by studying the chemistry of one such set of interactions and the bacterially produced small molecules that govern them. The central theme is farming, which insects like ants, beetles and termites have been doing for tens of millions of years. These studies can lead to new molecules and new biosynthetic pathways of interests to chemists and some insights into ecology and evolution for biologists.

Thursday, March 27, 2014

DR. KAVIRAYANI R. PRASAD

Indian Institute of Science

“Total Synthesis of Macrolactone Natural Products Palmerolide A and Sch725674”

ABSTRACT: Structurally diverse natural products with varied therapeutic properties progresses the drug discovery process at a rapid rate to an advanced stage. Natural products not only provide a vital lead in medicinal chemistry but also inspire synthetic organic chemists to synthesize the natural products, often keeping bio-activity profile and therapeutic potential in mind. Inspite of a wide array of synthetic methodolgies at the disposal, total synthesis of structurally complex natural products is far from perfection. In this lecture, I will outline our group’s effort in the application of simple tartaric acid and furfural, in the total synthesis of structurally complex macrolactone natural products palmerolide A, Sch725674 (fig. 1).

ABSTRACT: Over the past few years, significant research has been directed toward the development of new methods for synthetic efficiency and atom economical processes. Among them, the potential of transition-metal catalyzed reactions has been steadily demonstrated, as they provide a direct and selective way toward the synthesis of highly valuable products. We have been engaged in a project dedicated to the development of catalytic methods for the synthesis of bio-relevant targets. More specifically, we have been interested in hydrogenation and transfer hydrogenation reactions, which provide important catalytic approaches to fine chemicals. There is no doubt that chiral ligands are at the heart of any enantioselective homogeneous process. In this context, our contribution to this field is the development of atropisomeric diphosphanes named SYNPHOS and DIFLUORPHOS with complementary stereoelectronic properties. Some recent applications in this field will be presented.

Thursday, March 20, 2014

DR. ROLAND L. DUNBRACK

Fox Chase Cancer Center

“Structural Bioinformatics and Protein Structure Prediction”

ABSTRACT: The Protein Data Bank (PDB) provides a rich source of information when viewed as a whole. Statistical analysis of structural features from atom-atom contacts to biological and crystallographic interfaces have become a branch of modern bioinformatics and computational biology. We will present results of several studies that seek to improve our understanding of protein structure and our ability to predict structure from sequence, when an experimental structure is not yet available.

Thursday, March 13, 2014

DR. ABRAHAM NITZAN

Tel Aviv University (ISRAEL)

“Effects of Optical and Magnetic Interactions In Molecular Conduction Junctions”

ABSTRACT: Illuminated molecular junctions bring together a rich phenomenolgy involving the interplay between electron and energy transfer, plasmon-exciton interactions and spin transfer processes. Theoretical studies of several recently observed phenomena will be presented.

ABSTRACT: Most pathogens including bacteria, fungi, viruses and protozoa carry unique glycans on their surface. Currently, several vaccines against bacteria are marketed very successfully. Since many pathogens cannot be cultured and the isolation of pure oligosaccharides is extremely difficult, synthetic oligosaccharide antigens provide now a viable alternative. Based on the automated synthesis platform,1 that has now been completely overhauled, 2 we are currently developing multiple vaccine candidates against bacterial infections, fungi, and protozoan parasites. In addition to their function as antigens, the synthetic oligosaccharides serve as tools to create monoclonal antibodies, and to establish glycan microarrays to map vaccine epitopes.3 In this lecture B. anthracis, C. difficile and malaria will be used as examples to illustrate the approach.4-6

Traditionally, chemists have performed reactions in a batch-wise mode. In recent years continuous flow systems have become increasingly interesting to practitioners of synthetic chemistry. 7 Described is the use of a continuous flow system to produce the anti-malaria drug artemisinin in large quantities. 8,9

ABSTRACT: In polymer-based organic photovoltaics (OPVs), directional control over exciton migration and charge separation within the active layer, and efficient charge-harvesting at the donor- acceptor interface represent important goals in achieving OPVs with improved power conversion efficiencies. Crystalline nanofibers (or nanowires) of poly (3-hexylthiophene) have attracted a great deal of interest because of the potential for efficient exciton or charge migration along specific directions (transverse or parallel) with respect to the nanofiber axis, processes which strongly depend on the dominant coupling type (inter-chain or intra-chain) within the crystalline aggregate. Our research uses combined time-, polarization-, and wavelength-resolved photoluminescence spectroscopy and conducting probe AFM techniques to probe dynamics and electronic properties in isolated P3HT nanostructures (nanoparticles, nanowires, and most recently, chemically cross-linked branched nanostructures) to investigate how local microstructure might be tuned, and it's effect on optoelectronic properties. In particular, newly discovered branched cross-linked nanostructures show a significant spatial variation in internal packing order offering an interesting chemical platform to test hypotheses on the role of ordered-disordered chemical interface on intrinsic charge-separation in neat polymers.

ABSTRACT: The Krauss lab is involved in development of novel organic reactions, as well as the application of organic chemistry to HIV vaccine development and chemical glycobiology. To begin this seminar, we will discuss the development of cyclopropanated allylation reagents which exhibit homoallylation activity. Reacting through Zimmerman-Traxler transition states, these reagents selectively afford stereochemical patterns not easily accessed by other methods.

In the second part, we will describe a new method for design of carbohydrate HIV vaccines, which combines organic synthesis and directed evolution techniques. This work originates from the observation that some HIV positive individuals produce antibodies which are broadly neutralizing and protective against HIV infection.

One such antibody, 2G12, recognizes and binds to a cluster of carbohydrates on the viral envelope protein gp120. Our goal is to develop synthetic carbohydrate clusters which closely mimic the viral carbohydrate cluster, and which might thus elicit a 2G12-like antibody response when used as a vaccine. In order to design carbohydrate clusters which closely mimic gp120, we have developed evolution-based strategies, in which immobilized 2G12 is used to recognize and fish out the best glycocluster mimics of gp120 from amongst large libraries of ~10 trillion different glycosylated peptide- or DNA structures. The glycocluster structures obtained by these methods are recognized by antibody 2G12 as strongly as is the viral protein itself, and are thus of great interest for vaccine studies.

Tuesday, February 18, 2014

DR. ERNESTO FREIRE

Johns Hopkins University

“Thermodynamic Strategies in Drug Development: Small Molecules and Biopharmaceuticals”

ABSTRACT: (Not Available)

Thursday, February 13, 2014

DR. CHARLES N. McEWEN

University of the Sciences

“New Ways to Ionization Compounds for Analysis and Tissue Imaging by Mass Spectrometry”

ABSTRACT: Mass Spectrometry is a premier analytical method for the analysis of minute quantities of compounds in complex matrices. A successful analysis is dependent on producing gas-phase ions. The ability to produce gas-phase ions of nonvolatile and high-mass biological compounds earned the inventors of electrospray ionization (ESI) and matrix assisted laser/desorption ionization (MALDI) the 2002 Nobel Prize in Chemistry. These methods are highly successful, but require either high voltage or a laser to convert solid or solution phase compounds into gas phase ions. In this talk, new methods for converting volatile and nonvolatile, low and high mass compounds to gas-phase ions will be presented. These methods are highly sensitive, require little user expertise, and can eliminate the need for an ‘ion source’. A mechanistic approach will be discussed that led to discovery of matrix compounds that allow gas phase ions of molecules at least as large as the 66 kDa bovine serum albumin protein to be produced by exposure to the vacuum conditions available with any mass spectrometer. Some applications of these methods will also be presented.

Thursday, February 6, 2014

DR. JOHN P. PERDEW

Temple University (Physics Department)

“Climbing the Ladder of Density Functional Approximations”

ABSTRACT: Kohn-Sham density functional theory is the most widely-used method of electronic-structure calculation in materials physics and chemistry, because it reduces the many-electron ground-state problem to a computationally tractable self-consistent one-electron problem. Exact in principle, it requires in practice an approximation to the density functional for the exchange-correlation energy. Common approximations fall on one of the five rungs of a ladder, with higher rungs being more complicated to construct but potentially more accurate. The first three or semi-local rungs are important, because (a) they are computationally efficient, (b) they can be constructed non-empirically, and (c) they can serve as input to fourth-rung hybrid functionals. The third-rung meta-generalized gradient approximation can recognize and describe covalent, metallic, and weak bonds, providing a good description of the equilibrium properties of many molecules and solids.

Thursday, January 30, 2014

DR. RICHARD ZARE

Stanford University

"Advances in Ambient Ionization Mass Spectrometry"

ABSTRACT: I wish to describe two recent developments in my laboratory using ambient ionization mass spectrometry, a mass spectrometric technique in which the sample of interest is in open air at room temperature. The first concerns mass spectrometric imaging; the second concerns detection and identification of solution-phase reaction intermediates.

Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections) of the tissue at the specimen margin(s). We compare this to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 human cancerous and normal gastric tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, the Lasso method (multi-class logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The results obtained suggest that DESI-MSI/Lasso may be valuable for routinely assessing margins in gastric cancer surgery.

Palladium complexes catalyze a variety of oxidation reactions, including the Wacker oxidation, the oxidation of alcohols, and oxidative C-C bond-forming reactions. Simple Pd(II) salts react sluggishly with oxygen, but in the presence of suitable ligands or solvents, Pd complexes are capable of aerobic oxidation reactions. A key step in these reactions is the oxidation of Pd(0) by O2 to regenerate a Pd(II) intermediate. We have employed a battery of in-operando mass spectroscopic techniques such as desorption electrospray ionization mass spectrometry (DESI-MS, millisecond reaction times), electrospray ionization mass spectrometry (ESI-MS, minutes reaction times), and nano-electrospray ionization mass spectrometry (nanospray-MS, minutes reaction times) to search for reaction intermediates formed during the aerobic oxidation of 1,2-diols. By monitoring active reactions with mass spectrometry operating at various timescales, we have directly detected and identified a number of novel intermediates generated in solution during the fast alcohol oxidation and slow aerobic re-oxidation of (neocuproine)Pd(0). These studies reveal the formation of a novel trinuclear palladium complex, [(neocuproinePd(II))3(m3-O)2]2+. The identification of this previously unreported species provides new insights on the mechanism of aerobic oxidation mediated by Pd complexes.

Graduate Student Lectureship

Wednesday, December 11, 2013

DR. PAUL CREMER

Pennsylvania State University

"Exploring the Interactions of Cu2+ with Lipid Membranes"

ABSTRACT:

Biological membranes often contain negatively charged lipids such as phosphatidylserine, phosphatidylglycerol, phosphatidic acid, and gangliosides. The head groups of these lipids can strongly interact with positively charged amino acids from peptides and proteins (i.e. Arg and Lys residues), metal cation from the extracellular solution, as well as positively charged drug molecules. These negatively charged lipids are highly regulated within cells and are highly abundant in certain organelles while almost completely absent in others. Moreover, their concentration within a particular leaflet of a given membrane is often tightly regulated. Despite the high degree of control of lipid composition within cells, little is often known about the reason for it or even the specific nature of ligand-receptor binding interaction with such moieties. To remedy this, we have employed a combination of spectroscopic techniques (Figure 1), microfluidic platforms, monolayer and planar supported bilayer architectures to explore the specific biophysical chemistries of these interactions. This includes the development of a novel analytical tool that employs a pH sensitive fluorophore to probe subtle changes in the surface potential of lipid bilayers upon ligand or ion binding. Both thermodynamic and molecular level details of these systems have been obtained. The results reveal that binding can be highly dependent on the concentration of specific lipids within the membrane. Moreover, the presence or absence of various uncharged lipids can also greatly influence the binding properties. Interestingly, specific interactions involving hydrogen bonding, charge transfer, and hydrophobic interactions often dominate over simple electrostatic effects.

ABSTRACT: The complex biosynthetic pathways that afford asparagine-linked (N-linked) glycoproteins are now known to occur in all three kingdoms of life. The extremely varied and critical functions of N-linked glycosylation make this process of significant interest and importance in human health and disease and also of great relevance in medicine and biotechnology as protein therapeutics have become important elements in the modern pharmacopoeia. While many of the functions of N-linked glycosylation in prokaryotes are still unexplored, there is now compelling evidence that in selected prokaryotes, N-linked glycans play a critical role in bacterial pathogenicity by affecting immune system evasion, cellular adhesion, and host-cell invasion and colonization. This presentation will discuss current efforts to develop inhibitors as tools to probe the roles of glycosylation in pathogenic bacteria, methodological approaches for investigating the coordinated action of glycosylation pathway enzymes that function at the membrane interface in model membranes and in vivo, and the discovery of monomeric OTases from diverse prokaryotic sources as subjects for detailed biochemical and biophysical analysis.

ABSTRACT: Bacteria coordinate their behavior and defense mechanisms based upon small molecule signaling pathways. We have employed nitrogen-dense marine alkaloids as structural templates to design small molecules that short circuit bacterial defense mechanisms by disrupting two-component signaling pathways. These natural product mimetics are active against both Gram-positive and Gram-negative bacterial pathogens and are able to suppress both phenotypic antibiotic defense (biofilm formation) and genotypic antibiotic defense. The development of these small molecules will be presented, along with biochemical studies towards their mechanism of action and the application of these small molecules as adjuvants to breaking antibiotic resistance in vivo.

ABSTRACT: Transition metal catalysis has revolutionized organic synthesis by enabling new transformations with unprecedented selectivity. Often times, these processes rely on precious metals such as ruthenium, rhodium, iridium and platinum. Our group has been exploring more abundant first row transition metals as alternatives in catalysis. Open questions include – “how can the electronic structure of base metals be altered to achieve the reactivity more traditionally associated with heavier transition metals?” and “can the unique electronic structures of base metals be exploited for new transformations?” Our group has utilized redox-active ligands – those that undergo reversible electron transfer with the transition metal to enable two-electron chemistry with reduced iron and cobalt compounds. This approach has produced catalysts with superior activity and selectivity in reactions such as olefin hydrosilylation and hydrogen than established precious metal compounds. More recently we have focused on the discovery of new base metal precursors for high throughput catalyst evaluation. New phosphine-ligated cobalt compounds have been discovered for asymmetric hydrogenation, which demonstrate a new electronic structure paradigm in base metal catalysis. My lecture will focus on the application of base metal catalysis to important transformations and highlight the role of electronic structure on function and mechanism.

Thursday, October 24, 2013

DR. STEPHEN BENKOVIC

Pennsylvania State University

"A Perspective On Biological Catalysis"

ABSTRACT: With dihydrofolate reductase as a paradigm, we have examined the question of the importance of conformational changes and their contributions to catalysis. A variety of collaborative approaches that include nuclear magnetic relaxation, pre-steady state kinetics, fluorescence resonance energy transfer, phylogentically coherent events, stark effects and molecular dynamic simulations have focused on the parent and mutant forms of the enzyme. The collective findings support the presence of a network of residues within the protein fold that acts to generate a series of enzyme conformations along the reaction coordinate that optimize the reacting centers of the substrate and cofactor for the chemical transformation. They also allow comment on the conservation of protein dynamics throughout evolution.

Thursday, October 17, 2013

DR. SETH HERZON

Yale University

"Target-Driven Total Synthesis"

ABSTRACT: Natural products total synthesis provides a rich and unparalleled opportunity to develop new synthetic transformations, conceive novel and general strategies to access complex structures, and study the mechanism of action of bioactive targets. We have recently developed a general, unified pathway to synthesize the hasubanan and acutumine alkaloids, a large family of polycyclic botanical natural products. Our strategy to access these targets, and the total syntheses of ten members of this family, will be presented. In addition, we have developed a general and versatile route to prepare complex diazofluorenes, an unusual functional

group found in the antiproliferative metabolites known as the kinamycins and lomaiviticins. Applications of this chemistry towards the syntheses of kinamycin F and lomaiviticin aglycon, and elucidation of the mechanism of action of lomaiviticin A, will be presented.

ABSTRACT: Our laboratory is developing new tools to understand protein folding, conformational changes, and proteolysis. We have recently shown that the thioamide – a single-atom substitution of the peptide backbone – can be used as a probe to monitor structural changes in proteins by quenching fluorophores, including the natural amino acids tryptophan and tyrosine, and several unnatural amino acids. We have developed methods for incorporating the thioamides into full-sized proteins by chemically synthesizing peptides containing the thioamides, and ligating them to proteins expressed in E. coli cells. Donor fluorophores can be incorporated into the cellularly-expressed fragment using unnatural amino acid mutagenesis or post-expression labeling, so that double-labeled proteins can be generated with a minimum of unnecessary peptide synthesis. Development of these methods allows us to begin study of the role of protein motion in processes such as cell signaling and amyloid diseases. We have also adapted our fluorophore/thioamide pairs to make probes of proteolysis, using the minimally-perturbing nature of the thioamide to investigate cleavage at specific sequences. We have used these tools in vitro, and we are working to extend them to use in lysates and living cells.

Thursday, September 26, 2013

DR. ERIC SCHELTER

University of Pennsylvania

"Cerium and Uranium: Elements of Opportunity In Rare Earths Sustainability"

ABSTRACT: Pure rare earth elements, La–Lu, Y and Sc, are used in critical applications in modern electronics, optics, and renewable energy. The international market for the elements is currently in crisis following export restrictions by the Chinese government, due to environmental damage caused by the mining industry. Chemical problems in the supply chain, including dirty, inefficient beneficiation and separations, are primary to alleviating shortages. We have been expanding the fundamental synthetic chemistry of cerium and uranium to address problems in rare earths sustainability. In particular, we have developed their redox chemistry and chemistry of their highest oxidation states. The accessibility of the tetravalent configuration for cerium(IV) makes that element unique among the rare earths. This redox ability underlies its simple separations chemistry from mixtures of light rare earths and enables useful one-electron oxidation chemistry for applications in organic and inorganic syntheses and heterogeneous catalysis. New strategies for accessing and stabilizing cerium(IV) compounds, with potential applications for targeted separations of terbium and praseodymium will be presented. Fundamental uranium chemistry, including activation of uranyl compounds that are typically a component of mining waste, as well as organometallic and small molecule activation with uranium, will also be discussed.

Thursday, September 19, 2013

DR. GREGORY D. SCHOLES

University of Toronto

"Ultrafast Light Harvesting Processes In Photosynthesis"

ABSTRACT: Photosynthetic light harvesting complexes are sophisticated multichromophoric assemblies used to regulate and concentrate photo-excitations for delivery to reaction centers under wide-ranging incident irradiances [1]. They provide wonderful model systems for the study of energy transfer mechanisms in well-defined structures [2,3]. I will address the current status and issues regarding quantum effects and coherent ultrafast energy transfer in light harvesting complexes of cryptophyte algae.

ABSTRACT: In molecular aggregates, excited states (so called excitons) are coherently shared by a large number of molecules. This leads to unique linear and non-linear optical properties, such as ultrafast emission, narrowing of the lineshapes and efficient excitation energy transfer. Of particular interest are tubular aggregates which mimic the structure of the photosynthetic antenna complexes of green bacteria. They serve as model systems to study the photophysical processes occurring in light harvesting systems as well as the nature and dynamics of excited states in molecular assemblies of reduced dimensionality. However, theoretical modeling of their photophysical properties is a challenging task due to the complex interplay of the interactions involved and the number of molecules the typical aggregate contains.

We present new results on modeling of excited state dynamics in self-assembled TPPS4 nanotubes (see Fig. 1). We take into account all the relevant interactions, namely: (1) intermolecular resonance inter- actions, (2) intermediate-strength linear coupling of electronic excita- tions to one effective intramolecular mode, (3) the influence of static disorder, and (4) the interactions

with the continuum degrees of freedom in the environment. We combine the two- particle approximation for the description of the intermediate-strength vibronic coupling [2] with Monte Carlo simulations of the static disorder and Pauli master equation treatment of the coupling with the environment.

Our approach properly accounts for the contributions to the linewidths arising from both the static disorder and dephasing. We apply it to model absorption and linear dichroism spectra of the TPPS4 nanotubes. We find good agreement with the

experimental data, and are able to explain the mechanism responsible for the lack of

temperature dependence of absorption linewidths, as well as a very low fluorescence quantum yield, observed in the recent experiments. This understanding opens up the perspective for studies of the ultrafast excited state dynamics and exciton diffusion.

“Variations Around the Carbo-Benzene Core. The Effect of Substituents”

ABSTRACT: Functionalization of carbo-mers through the introduction of various substituents onto their expanded skeleton allows potential applications to be envisioned in different domains [1]. The synthesis of amino-substituted carbo-benzenes [2,3] and fluorene-substituted counterparts [4] have been recently investigated and will be described. The properties of these cyclic macro-aromatic carbo-benzenes will be discussed and compared with those of their carbo-butadiene acyclic references. The effect of the substituents on the stability and reactivity of the carbo-benzenic macrocycle will be more particularly described.

ABSTRACT: Motivated by atmospheric aerosol chemistry of marine and urban regions and biophysical applications related to lung lining and biomembranes, monovalent and divalent cations and anions were investigated using phase sensitive sum frequency generation (PS-SFG) spectroscopy to understand the surface propensity and availability for reaction at water surfaces. Ion valency, polarizability, size, shape, and identity of the counterion are critical factors in considering ion organization and subsequent changes in interfacial electric field at the air water interface. Phospholipids and fatty acids were also studied using both SFG and Brewster angle microscopy (BAM). Head group differences, especially with regard to hydrogen bonding capability and extent, are discerning factors for surface organization and shape distinction at the water surface.Friday, April 26, 2013

DR. TREVOR DOUGLAS

Montana State University

"Packing Them In: Using Self-Assembled Protein Cages to Direct the

Synthesis and Packaging of Polymers, Minerals, and Proteins"

ABSTRACT: Protein cages have emerged as useful platforms for synthetic manipulation with a range of applications from materials to medicine. Synthetic manipulation can impart new function, combining the best of evolution and directed synthetic design. We have developed a library of protein cage architectures, which differ in size, porosity, and stability, for synthetic manipulation. This library of cages include ferritins (and ferritin-like proteins), virus capsids, and heat shock proteins. Ferritins, derived from hyperthermophiles, are stable to temperatures above 100ºC and are useful in the synthesis of magnetic and semiconducting nanoparticles. The unique scaffold-templated self-assembly of the bacteriophage P22 capsid has been utilized for the directed synthesis and packaging of a range of gene products as well as organic, and inorganic, polymeric materials. The use of virus capsids has resulted in a paradigm shift from the study of viruses as disease causing agents to their realization as highly useful supramolecular assemblies, which can be chemically and genetically modified.

The packaging of material on the inside of the protein cages can dramatically change the physical properties of both the cage and the encapsulated cargo. We are investigating the effects of molecular crowding on encapsulated enzymes and polymers, the effects of the protein cage on the surface properties of encapsulated magnetic materials, and the influence of the encapsulated cargo on the physical properties on these composite materials. We are developing a wide range of bio-inspired composite materials that integrate protein architecture with organic and inorganic synthetic components. In particular, the use of these protein cage nano-materials as targeted therapeutic and diagnostic agents and as controlled nano-reactors will be discussed.

ABSTRACT: A key issue in the use of nanomaterials is controlling how they interact with themselves and with the outer world. Our research program focuses on the tailoring of nanoparticles of surfaces for a variety of applications, coupling the atomic-level control provided by organic synthesis with the fundamental principles of supramolecular chemistry. Using these engineered nanoparticles, we are developing particles for biological applications, in particular delivery and sensing. This talk will focus on the interfacing of nanoparticles with biosystems, and will discuss our use of nanoparticles for delivery applications including our in vitro studies of small molecule, nucleic acid, and protein delivery. This presentation will also feature the use of nanoparticles for diagnostic applications, including the use of array-based sensing paradigms for the sensing and identification of proteins, bacteria and cell type and state.

Thursday, April 18, 2013

DR. BARRY COOPERMAN

University of Pennsylvania

“Probing Protein Synthesis Dynamics With Fluorescent Probes”

ABSTRACT:

Graphic that describes the seminar:

Brief Abstract: Despite substantial recent progress, our knowledge of the dynamics of the protein synthesis machinery remains incomplete. Some comparatively simple questions remain unresolved. We address these questions through joint application of ensemble and single molecule fluorescence (SMF) approaches. These methods, which have different advantages and limitations, provide strong complementarity in the results they produce, allowing elucidation of many aspects of the mechanism of protein synthesis, both in vitro and in live cells.

Thursday, April 11, 2013

DR. FRANZ GEIGER

Northwestern University

"The Acid Base Transparency of Graphene"

ABSTRACT: Acid base chemistry at surfaces and interfaces is important in a variety of applications in chemistry, physics, biology, and materials science. From a fundamental perspective, and because of its ubiquity in nature, acid/base chemistry at fused silica/water interfaces has been studied quite extensively by theory and experiment,and two acid/base equilibria linking the surface-localized species SiOH2+, SiOH, and SiO- are now well established. Motivated by the importance of graphene in fundamental studies and various applications involving aqueous-solid interfaces, we study here whether acid base chemistry at fused silica/water interfaces can be suppressed in the presence of graphene. We apply second harmonic generation (SHG), Raman spectroscopy, vibrational sum frequency generation (SFG), optical microscopy, contact angle goniometry, and scanning tunneling microscopy (STM) to exfoliated graphene sheets deposited on fused silica flats, and find that the interfaces respond to changes in bulk solution pH largely as if the graphene were absent. This finding suggests that proton diffusion through graphene may be facile under the conditions of the experiment (room temperature, 10 mM NaCl solutions adjusted to pH values between 3 and 10). The implications of these results for applications using graphene at fluid/solid interfaces are discussed.

Thursday, March 28, 2013

DR. CHRISTIAN ROJAS

Barnard College

"Nitrene-Mediated Amino Sugar Synthesis"

ABSTRACT: Intramolecular nitrogen insertion reactions provide stereoselective routes to a range of 2-amino sugars. In our approach, acyl nitrenes, including metal-complexed species, serve as nitrogen-atom donors within glycal frameworks. Glycal azidoformates, primary carbamates, and N-hydroxycarbamates are the nitrene and metallanitrene precursors, and formation of a glycosyl aziridine intermediate enables in situ glycosylation with high anomeric stereoselectivity. There are significant differences in stereo- and chemoselectivity among the four diastereomeric D-glycal substrates, but the process can be controlled through proper choice of protecting groups, solvent, and catalyst. The overall process constitutes an amidoglycosylation reaction of glycals, and our studies also help delineate fundamental reactivity properties of acyl nitrenes and nitrenoids.

ABSTRACT: Terahertz spectroscopy has proven itself to be an excellent non-contact probe of charge injection and conductivity with sub-picosecond time resolution. One may exploit this capability to study a variety of materials, and here we choose to probe the transient photoconductivity of dye-sensitized nanostructured wide band gap semiconductors photosensitized by high-potential chromophores. These systems are of interest in the area of renewable energy research and artificial photosynthesis.

I will discuss the charge injection time scale and efficiency for a selection of high-potential photoanodes (HPPAs) for photo-electrochemical cells (Figure 1). The anodes consist of tris-pentafluorophenyl free-base and metallo-porphyrin sensitizers anchored to TiO2 and SnO2 nanoparticles either directly or axially. THz spectroscopic studies demonstrate the sensitizers used in these HPPAs are capable of injecting electrons into the conduction band of the metal-oxide materials in those cases where the energies of the donor (excited state dye) and acceptor (metal oxide conduction band minimum) components are appropriate. Importantly, the potentials photogenerated at the anode surface are high enough to permit the oxidation of high-potential electron sources.

I will also describe recent efforts, both experimental and computational, to probe and understand low frequency vibrational modes in organic molecular crystals. Calculating these modes has proven challenging because of the large influence of weak van der Waals interactions which are difficult to treat computationally for periodic systems, i.e., crystals. In addition, a new way to compare results from different calculations will be presented.

Figure 1. Part (a) shows the structure of the tris-pentafluorophenyl metallo-porphyrins studied. Part (b) displays their dichloromethane solutions where M = Ni2+, Cu2+, Pd2+, Zn2+, and H2 in going from the bottom to the top. Part (c) shows a high-potential Zn porphyrin axially complexed to isonicotinic acid that is anchored to a metal oxide surface.

Thursday, March 14, 2013

DR. YONG-ROK KIM

Yonsei University (KOREA)

New Methods for C-C Formation With Zinc and Palladium"

ABSTRACT:

Reactive oxygen species (ROS) have been a leading subject in chemical, environmental, and bio-medical science because of their unique physicochemical properties and highly reactive nature. ROS readily induce both positive and negative effects by the involvement with metabolism of cells and organs due to the superior reactivity and selectivity.1 In a field of life science, there are many applications of ROS such as photodynamic cancer therapy, blood product decontamination, water disinfectant, drug delivery system, and stereo-selective drug synthesis.2

The photophysical factors determining the efficiency of transient ROS generation has been investigated in terms of the molecular structures and electronic properties. In particular, the photo-induced ROS production initially consists of two different types (O2- and 1O2). The nature and functionality of the two critical species are distinctively examined. Based on the investigation, the fabrication strategy for the multifunctional composite materials, which generate ROS, is established for specific medical and environmental applications.3 In the presentation, recently fabricated multifunctional composite materials are introduced along with their excellent photo- induced functionalities for the targeted applications.4-7

“Model Studies on Heterogeneous Catalysts at the Atomic Scale: From Supported

MetalParticles to Two‐dimensional Zeolites”

ABSTRACT: Understanding catalysis, and in particular heterogeneous catalysis, has been based on the investigation of model systems. The enormous success of metal single crystal model surface chemistry, pioneered by physical chemists, is an outstanding example. Increasing the complexity of the models towards supported nano particles, resembling a real disperse metal catalyst, allows one to catch in the model some of the important aspects that cannot be covered by single crystals alone. One of the more important aspects is the support particle interface. We have developed strategies to prepare such model systems based on single crystalline oxide films which are used as supports for metal and oxide nano particles, whose geometric structure, morphology, electronic structure, as well as interaction and reaction with molecules from the gas phase may be studied at the atomic level. After a general introduction to model studies in catalysis, results from different research areas are presented: a) adsorption and reaction on nano particles supported on thin oxide films; b) 2D‐3D‐morphology, geometric, and electronic structure of supported metal nano particles partially in relation to doping of the support, c) strong metal support interaction (SMSI); and d) adsorption and reaction on two‐dimensional silicates and alumino‐silicates in ordered and vitreous phases.

Thursday, February 28, 2013

DR.WEI-DONG YANG

Temple University (Biology Department)

ABSTRACT: The flow of genetic information is regulated by selective nucleocytoplasmic transport of individual messenger RNA:protein complexes (mRNPs) through the nuclear pore complexes (NPCs) of eukaryotic cells. Yet, the nuclear export kinetics, three-dimensional (3D) pathway, and selectivity step of mRNPs transiting an NPC remain obscure. Here we employ single-molecule fluorescence microscopy with an unprecedented spatiotemporal super-accuracy of 8 nm and 2 ms combined with Monte-Carlo simulations to unveil these mechanistic fundamentals of nuclear mRNP export in live human cells. We find that mRNPs exiting the nucleus are decelerated and selected at the center of the NPC, and adopt a fast-slow-fast diffusion pattern as they translocate through the NPC. Approximately 34% of all mRNPs successfully transit during their brief, ~12-ms interaction with the NPC, a fraction strikingly close to the 50% export efficiency of their export receptor Tap-p15. A 3D mapping of export routes for individual mRNPs indicates that mRNPs primarily interact with the periphery on the nucleoplasmic side and in the center of the NPC, without entering the central axial conduit utilized for passive diffusion of small molecules, and eventually dissociate on the cytoplasmic side.

Thursday, February 21, 2013

DR. KENNETH KARLIN

Johns Hopkins University

"Copper and Heme-Copper Complex O2 Reactivity: Bioinorganic Aspects”

ABSTRACT: Copper proteins, including heme/Cu containing cytochrome c oxidase (CcO), process dioxygen in biological systems, functioning in O2-transport, oxygenase activity (i.e., O-atom insertion into organic substrates) and O2-reduction to hydrogen peroxide or water. A brief overview of some of the relevant protein chemistry will be presented. Our research aims to contribute to a fundamental understanding of O2-reactivity at copper or heme/Cu centers via the examination of synthetically derived chemical model systems. In this context, results from particular recent chemical studies will be described: (i)The reactivity of mononuclear copper-superoxide or hydroperoxide species, i.e., CuII(O2•–) and CuII(–OOH), respectively, is of considerable current interest. Recent results concerning formation of such complexes and their substrate oxidation chemistry will be presented, in fact illustrating that these species can effect certain kinds of O-H or C-H hydrogen-atom abstraction reactions. (ii) Model systems for CcO O2-binding and reduction are being pursued and dioxygen reactions with reduced (heme)FeII…CuI ensembles lead to peroxo-bridged FeIII-(O22–)-CuII complexes. These have been characterized by a variety of spectroscopic or physico-chemical approaches. The significant effect of the nature of the porphyrinate or ligand for copper ion on the FeIII-(O22–)-CuII structure and physical properties will be emphasized.Results concerning O-O reductive bond cleavage in a FeIII-(O22–)-CuII systems will also be described.

Thursday, February 14, 2013

DR. PATRICK WALSH

University of Pennsylvania

ABSTRACT: The polar Felkin-Anh, Cornforth, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected hydroxy aldehydes and ketones proceeds via a non-chelation pathway. This prediction has held true for the vast majority of additions reported in the literature and few methods for chelation-controlled additions of organometallic reagents to silyl-protected hydroxy aldehydes and ketones have been introduced. Part 1 of this lecture will introduce a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri- and (Z)-disubstituted vinylzinc reagents to a- and b-silyloxy aldehydes and ketones using alkyl zinc halide Lewis acids, RZnX, to give chelation-controlled products (dr ≥18:1). Part 2 will outline a variety of new C–C bond forming reactions catalyzed by palladium complexes that involve in situ formation of the organometallic component via deprotonation of weakly acidic hydrogens (pKa as high as 35!) under catalytic cross-coupling conditions.

ABSTRACT: Advances in fluorescence microscopy had a pivotal impact in cellular and molecular biology. The advent of two-photon excitation (2PE) microscopy pushed to design new instruments and experiments. This also allowed to experience new 3D imaging modalities from single molecule to organ studies [1]. Recently, “super resolution” and "optical nanoscopy” approaches have been implemented in a variety of far-field optical microscopes. In order to further improve the performances of 2PE we focused different super resolution approaches and combined architectures. IML-SPIM (Individual molecule localization selective plane illumination microscopy) [2] has been combined with 2PE towards imaging of 3D thick specimens [3]. 2PE-STED has been adapted to 2PE-SW-STED utilizing a single wavelength (SW) both for two-photon excitation and depletion [4]. Interesting variations on the theme are related to the more general RESOLFT concept extending its utilization to lithography [5]. Multimodality can be extended to scanning probe methods [6], while 3D imaging of cellular aggregates and thick specimens is the main goal of our developments. So far, a variety of architectures will be critically outlined in regard to different applications demanding for investigations at the nanoscale.

ABSTRACT: I will discuss two recent experimental developments in our group. Fast Relaxation imaging combines microscopy with small laser-induced temperature jumps to study biomolecules inside cells as they fold or bind. Examples include the folding dynamics and stability of proteins inside living cells, as well as protein-protein interactions such as the latent heat shock response. From individual cells, I will then move up to chemical probing of tissues. Here, a variant of coherent anti-Stokes Raman scattering, which we call NIVI (near-infrared vibrational imaging) provides the best of several worlds: fast data acquisition, linear background-free signals from a non-linear technique, and 99%+ diagnostic reliability in a rat model of breast cancer.

Thursday, January 31, 2013

DR. MARK A. RATNER

Northwestern University

“Molecular Mesoscopics: Transport In Molecular Junctions”

ABSTRACT: The two phenomena of electron transfer in molecules and electron transport through molecules are closely related to one another. Some of the phenomena exhibited in one of these areas can be mirrored in the other, but there are also differences. In this talk, we discuss the transport situation and different mechanisms for transport that occur under different temperature conditions and with different molecular structures. In particular, we will examine transport through more complex organic molecules than usual, and the interference phenomena that can result from cross-coupling, from meta linkages, and from simultaneous transport through more than one molecule. Emphasis will be conceptual (no complicated equations, no harping on methodology), and some concepts of physical organic chemistry, and their relationship to transport, will be addressed.

Thursday, December 6, 2012

DR. HERMAN SINTIM

University of Maryland

"Using Small Molecules To Have A Meaningful Conversation With Bacteria"

ABSTRACT: In the last two decades scientists have come to realize that bacteria rarely live in isolation but rather live in communities of other bacteria, called biofilms, as well as amongst the cells of higher organisms. Due to evolutionary pressure and the stringency of the immune surveillance, bacteria have learned to make decisions after a quorum is reached. This population-dependent bacterial communication, known as quorum sensing, first starts with the synthesis of small molecules (which could be considered as virulence factors), followed by perception of these molecules and the triggering of nucleotide signaling (such as c-di-GMP, c-di-AMP etc) leading to the biofilm phenotype or toxin production. Understanding the interplay between the various signaling molecules would therefore provide the framework for the design of next-generation anti-infectives. In this talk, I will highlight some of the newest advances made in both quorum-sensing and c-di-GMP signaling in bacteria and demonstrate how elucidations of these key processes in bacteria have led to the development of new small molecules that could be used to "quench" bacterial "small" talk. Both biochemical processes, as well as the syntheses of small molecules would be discussed.

Thursday, November 29, 2012

DR. MICHAEL DOYLE

University of Maryland

“New Catalytic Stereoselective Methods for Synthesis”

ABSTRACT: Dirhodium(II) compounds are highly effective catalysts for a broad range of chemical transformations. Some of the advantages of these catalysts (and their copper counterparts) for chemical syntheses involving metal carbene reactions of diazoacetates and aryldiazoacetates (cyclopropanation, C-H insertion, ylide formation and reactions) have been described, and high enantioselectivities have been achieved. Their Lewis acidity is suitable for single-point binding of Lewis bases whose activation is catalytic for cycloaddition reactions with off-rates that enhance turnover numbers. This presentation will focus on our newest discoveries in two applications: catalytic reactions of enoldiazoacetates and beta-ketodiazoacetates, as well as Lewis acid catalysis, all involving dirhodium catalysts. Control of reactivity and stereoselectivity is inherent in the catalyst that is employed. Diversity in product formation from specific reactants due only to the selection of catalyst will be presented, and the utility of dirhodium catalysis for complex and highly selective transformations of vinylcarbene intermediates will be discussed. Thursday, November 8, 2012

DR. RONNIE KOSLOFF

Hebrew University of Jerusalem

“Ultrafast, Ultracold Chemistry”

ABSTRACT: Atoms and molecules at temperatures below one milli-Kelvin can only be understood as quantum mechanical objects - they represent the extreme quantum limit. At these temperatures quantum interference effects are not washed out by thermal averaging, the state of matter is almost pure and well characterized. For this reason ultracold matter becomes an ideal candidate for coherent control which relies on interferences between matter waves. Such conditions make experiment and theory converge allowing a direct test of controllability. Ultrafast: The wave particle duality is a corner-stone of the interpretation of physical reality. Coherent control has emerged from the appreciation of the wave nature of matter. In a nutshell, coherent control employs constructive interference to steer the outcome of a dynamical process to a desired one while suppressing undesired outcomes by destructive interference. Ultracold: The capability to cool matter to temperatures very close to the absolute zero is one of the hottest topics in contemporary physics. Such forms of matter exist in the extreme quantum regime where the de Broglie wavelength of a single atom can extend to macroscopic dimensions. When the wavelength of the atoms exceeds the average inter-atomic separation their individual identity is lost. This is the source of macroscopic quantum effects such a Bose-Einstein condensation (BEC) and Fermi degeneracy. The phenomenon is not limited to atoms. Ultracold molecules have been produced from cold atoms through photoassociation and from an atomic condensate by Feshbach resonances. Ultracold ion-molecule chemical reactions have been reported in laser cooled Coulomb crystals in ion traps. These chemical phenomena are the twilight of the dawn of a new era of Ultracold Chemistry. The quantum nature of cold matter requires novel tools of chemical synthesis, naturally leading to coherent control as the basic synthetic scheme.

ABSTRACT: Intrinsically disordered proteins are involved in a range of functional roles in the cell, as well as being associated with a number of diverse diseases, including cancers, neurodegenerative disorders, and cardiac myopathies. We use single molecule fluorescence approaches to characterize disordered proteins implicated in the progression of Parkinson's and Alzheimer's diseases. Our goal is to understand how disease-associated modifications to these proteins alter their conformational and dynamic properties and to relate these changes to disease pathology.

Thursday, October 25, 2012

DR. GEORGE CHRISTOU

University of Florida

“Manganese Carboxylate Cluster Chemistry: From Models of the Photosynthetic

Oxygen-Evolving Complex to Molecules as Nanoscale Magnets…”

ABSTRACT: There is a longstanding interest in higher oxidation state manganese carboxylate chemistry in our group that has been stimulated and driven by the various areas of relevance of MnIII,IV coordination chemistry. Two of these are: (i) the ability of many polynuclear Mn clusters to function as single-molecule magnets (SMMs), i.e., molecules that behave as nanoscale magnets at low temperatures by exhibiting magnetization hysteresis loops, the diagnostic classical property of a magnet. SMMs thus represent a bottom-up, molecular approach to nanomagnetism. They also display interesting quantum properties such as quantum tunneling of magnetization (QTM), and have consequently been proposed as molecular components of spin-based quantum computation and spintronics devices; and (ii) the oxygen-evolving complex (OEC), is part of the photosynthesis apparatus of green plants, cyanobacteria and algae, and is now known to be a heterometallic oxo-bridged Mn4Ca cluster with primarily carboxylate ligation and comprising a Mn3CaO4 distorted-cubane attached to an extrinsic Mn,. Synthesis of this unit in the laboratory has been a major objective of many groups during the last quarter of a century, including our own. Both areas involve, among other things, development of synthetic methods to new Mn-oxo clusters and their modification, and detailed magnetochemical analysis of obtained products. This talk will overview some of our recent results in both these areas, including a) supramolecular aggregation of SMMs into ‘clusters-of-SMMs’ with deliberately very weak (but non-zero) inter-SMM interactions (one product is shown) and their resulting structural and quantum properties, and b) attempts to synthesize the OEC, together with the magnetic and other spectroscopic properties of the obtained compounds.

Thursday, October 18, 2012

DR. DAVID SHERMAN

University of Michigan

“De Novo Design in Chemical Catalysis: Endless Inspiration

from Natural Product Pathways”

Over the past decade, we have expanded our analysis and engineering of a broad class of monooxygenases from diverse natural product pathways. Cytochrome P450s and flavin oxidases are among the most widely distributed groups of enzymes in nature, catalyzing the oxidation of natural product and xenobiotic small molecules. Although hundreds of monooxygenases have been examined in the oxidative metabolism of drugs, only a small number have been studied in bacterial and fungal secondary metabolism, especially in macrolide antibiotic biosynthetic pathways. In most of these systems, hydroxylation and/or epoxidation reactions occur in the late stages of biosynthesis after macrolide formation by the polyketide synthase (PKS). In addition to significant increases in biological potency, hydroxylation provides potential sites for chemical modification and further enhancement of bioactivities. Thus, the creation of novel macrolide analogs through in vivo metabolic engineering and in vitro chemoenzymatic synthesis warrants a concomitant effort towards the development of monooxygenases with defined substrate specificities. Over the past several years, our work has focused on expanding knowledge of substrate flexibility and functionality of a range of P450 monooxygenases from macrolide and selects other natural product systems, including fungal alkaloids. Our progress has provided fascinating new insights into the molecular mechanisms of these biocatalysts, and their ability to generate novel products by hydroxylation, epoxidation, pinacol rearrangements, pyran ring formation and other transformations operating on both natural and unnatural substrates. This information is directing protein engineering/substrate engineering efforts to better understand the function and positional specificity of individual enzymes, as well as their ability to catalyze a range of oxidative reactions. Our program brings complementary approaches of synthetic chemistry to create diverse substrates, biochemistry to investigate and develop engineered monoxygenases with versatile substrate selectivity, and X-ray and NMR-based methods to obtain high resolution structural information for mechanistic understanding of these remarkable proteins.

ABSTRACT: Two areas of focus in the Kelleher lab are natural products discovery and chromatin oncobiology. While seemingly disparate research aims, our lab has developed a screening method to test the epigenetic activity of novel natural products, thereby merging the two fields. We have developed a strategy utilizing mass spectrometry-based proteomics as a screen of culturable bacilli, actinomycetes and even fungi for expression of NRPS/PKS enzymes. The screen uses the PrISM technology (short for Proteomic Investigation of Secondary Metabolism), published in 2009 (Bumpus, Evans, Thomas et al., Nat. Biotechnol., 2009, 10, 951-956) to survey for expression of large thiotemplated enzymes in endogenous proteomes of hundreds of strains across several lab growth conditions. We now have a sense for what types of clusters can be detected using PrISM and have improved the technology for its application to strains and clusters with both known and unknown genomes. This platform is ideal to feed directly into a recently reported new method capable of direct determination ofcombinatorial methylation kinetics in vivo. In initial studies with this methodwe have used cell lines with aberrant histone H3 methylation patterns derived from a patient withMultiple Myeloma to study how methylation states on lysines 27 and 36 are established and maintain the cancer phenotype (Zheng, Martinez-Garcia, Popovic et al., PNAS, in press). To understand how histone methylation patterns areestablished and maintained is critical to the field ofepigenetics and this same technique can be used to determine the biological activity of newly discovered natural products.

A Lesson on Better Taking Published (Stereo)Structures Not Always as Granted”

The asymmetric dihydroxylation of an allylic chloride, which we derived from an enynol intermediate of the Hoffmann-La Roche synthesis of vitamin A, and another 8 steps furnished the hydroxyethylated furanone (R)-1 with 92% ee. An oxidation with MnO2 delivered the furanone (+)-(R)-2 in 50% yield. (R)-2 was the accepted structure of (+)-gregatin B, the first synthesis of which we had set out to accomplish. However, our specimen of synthetic (+)-(R)-2 exhibited different methyl singlets in the 1H-NMR spectrum than (+)-gregatin B. This showed that the constitution of gregatin B was distinct from 2.

Normally, this situation would have left one wondering what else (+)-gregatin B could be. Yet, as luck would have it, the answer already emerged from our synthesis of (+)-(R)-2. This is because its ultimate step delivered not only 50% (+)-(R)-2 but also 2.6% of the isomer (+)-(R)-3 and the 1H-NMR spectrum of (+)-(R)-
3 displayed the same methyl singlets as (+)-gregatin B. A different strategy allowed a deliberate rather than serendipitous synthesis of (+)-gregatin B as well as synthesizing related natural products. We thereby reassigned the constitution of 6 compounds, revised the configuration of their quaternary carbon in 5 cases, and elucidated the configuration of 4 previously unassigned stereocenters. Analogous structure reassignments are due for further natural products.

Thursday, September 27, 2012

DR. SQUIRE BOOKER

Pennsylvania State University

“A Radical-Dependent Strategy For Methylation of rRNA Leading To Antibacterial Resistance”

ABSTRACT: Elaborations of unactivated carbon centers are among the most demanding reactions that enzymes catalyze. These reactions generally involve radical intermediates, often produced by strategic abstraction of substrate hydrogen atoms (H•s). A distinct strategy, predominant in the anaerobic world and also important in aerobes, employs a 5’-deoxyadenosine 5’-radical (5’-dA•), derived from a reductive cleavage of S-adenosylmethionine, as the H• abstractor. In all enzymatic reactions in which H• abstraction from an unactivated carbon center has been demonstrated unequivocally, the carbon center has been sp3-hybridized. However, reactions involving the functionalization of sp2-hybridized carbons centers are increasingly observed, especially within the radical SAM superfamily of enzymes. This talk will highlight strategies employed by radical SAM enzymes to functionalize sp2-hybridized carbon centers, with particular focus on two enzymes, RlmN and Cfr, that methylate carbons 2 and 3, respectively, of 23S rRNA.

ABSTRACT: Phospholipase A2 (PLA2) is an enzyme catalyzing cleavage of carboxylic ester linkages on the sn-2 position of phospholipids, yielding fatty acid and lysophospholipid [1]. This enzyme plays important roles in the functionality of cell membranes, such as cell metabolism and signal transduction. To understand its hydrolysis mechanism at a molecular level, in the present study, the kinetics and mechanism of the enzyme reaction on supported lipid bilayers have been evaluated by in situ sum frequency generation (SFG) spectroscopy [2] and atomic force microscopy (AFM) [3].

Based on the high catalytic selectivity of PLA2 toward L-enantiomer lipids, five kinds of supported bilayers made of L- and D-dipalmitoylphophatidylcholine (DPPC), including L-DPPC (upper layer adjacent to solution)/L-DPPC (bottom layer) (or L/L in short), L/D, D/L, D/D and racemic LD/LD, were prepared on mica surface, to reveal the mechanism of the PLA2-catalyzed hydrolysis in detail [2-3].

AFM observations for L/L bilayer show that the hydrolysis rate for L-DPPC is significantly increased by PLA2 and most of the hydrolysis products leave substrate surface in 40 min. As D-entiomers are included in the bilayer, the hydrolysis rate is largely decreased in comparison with L/L bilayer. The total hydrolysis time of the supported bilayers by PLA2 increases in a sequence of L/L, L/D, LD/LD, and D/L (D/D is inert to the enzyme). D-entiomers finally remain on the mica surface at the end of the reaction. The hydrolysis catalyzed by PLA2 preferentially occurs on the perimeters of pits or defects in the bilayer surface. The bilayer structures are preserved during the hydrolysis process. Our kinetics model demonstrates that PLA2 mainly binds with lipids on the defect perimeters in the upper leaflet where the hydrolysis occurs: L-DPPC in upper leaflet is hydrolyzed to products and desorbed from the substrate; the lipid molecule underneath immediately flips up to upper leaflet to keep the bilayer surface hydrophilic. The model simulation suggests that PLA2-inactive D-DPPC in the enantiomer hybrid bilayers can significantly reduce the hydrolysis rate by the ineffective binding with PLA2.

Detailed discussions for the kinetics and mechanisms of the PLA2-induced hydrolysis reaction will be given based on these AFM and SFG observations.

ABSTRACT: In the macroscopic world, the movement of rotation is at the source of many examples
of machines and motors. Recent advances in the imaging and manipulation of single molecules
has stimulated much interest in the synthesis of molecules exhibiting unique
mechanical properties. Technomimetic molecules[1] are molecules designed to imitate macroscopic objects at the molecular level, also transposing the motions that these objects are
able to undergo. In this talk we will present the preparation and single-molecule study on functional nanovehicles i.e. molecular vehicles capable to transport a cargo and unidirectional
molecular motor.
The nanovehicles[2] with two (wheelbarrow in this case) or four triptycene[3] wheels are
assemble around a polycyclic aromatic hydrocarbon platform. The molecular motor[4] is built around a ruthenium center coordinated to a cyclopentadienyl ligand terminated with five ferrocene electroactive groups. The design is similar to the electrostatic motor developed by Benjamin Franklin two and half centuries ago. The synthesis of the motor will be presented as well as variable temperature NMR experiments, STM study and electrochemistry studies showing its adequacy to act as a unidirectional molecular motor and proving some gearing motions[5].

ABSTRACT: After having solved the structure Self Assembled Monolayers (SAMs) of thiols on gold in 2008 [1] we have moved on to study the application of self-assembly of organic complex molecules (DNA, RNA and protein) on the same surface.

To do this we use atomic force microscopy (AFM)-based nanolithography, a technique called NANOGRAFTING, invented by G.Y. Liu in 1997, which consists of stimulating with the tip of an AFM the self-assembly of the organic polymers, properly terminated with a thiol linker, in a monolayer of a protein-repellent molecule, the choice of which is restricted at present to a thiol functionalized poly-ethylene-glycol. It turns out that the AFM-stimulated assembly produces monolayers (which we call NAMs to contrast them with the well known SAMs) that are much more compact and structurally sound than spontaneous SAMs. We use then the embedding bio-fouling SAM as a reference for differential measurements of the nanopatch properties upon reaction with other (bio)molecules.

We have applied these nanostructures to the following problems: 1) the first realization of an Elisa-type test on the nanoscale for single/few cells proteomics [2] 2) the orientation of intrinsically disordered proteins (i.e.prion proteins, alpha-synuclein) on surfaces using site-specific antibodies [3] and 3) the first measurement of the kinetics of helicase-type enzymes of human cells [4] .

[1] A. Cossaro et al., SCIENCE 321 (2008) 945

[2] F. Bano et al., NANOLETTERS 9 (2009) 2614

[3] B. Sanavio et al., , ACS Nano 4 (2010 ) 6607

[4] P. Parisse et al., (submitted to JACS)

Thursday, July 12th, 2012

DR. CAROLE BEWLEY

National Institutes of Health

“From Nature to Virtual: Chemistry, Biology and Discovery of Anti-Infectives”

ABSTRACT: Historically Nature has provided, or been the inspiration for, the majority of small molecules that are currently used as antibiotics and antitumor agents. Research in the Bewley group encompasses chemical, biological and structural studies of natural products, as well as small molecules and proteins that inhibit viral entry or the growth of bacterial pathogens. We will discuss two ongoing projects in the group including i. discovery of antibacterial natural products from rare or under-studied marine invertebrates, and ii. structural and mechanistic studies of HIV entry inhibitors. Each will provide examples of how we use multi-disciplinary approaches to address biological questions relevant to infectious diseases.

ABSTRACT:In his seminar, Prof. Rosenzweig will describe the synthesis and application of InP/ZnS luminescent quantum dots in enzyme assays. The structural, and optical properties of InP based quantum dots will be compared to the properties of the more widely used CdSe-based quantum dots. Prof. Rosenzweig will describe the encapsulation of InP/ZnS quantum dots in liposomes to form highly bright, and cell permeable luminescent liposomes, and the application of these luminescent liposomes to quantitatively determine the enzyme activity of phospholipases and the potency of phospholipase inhibitors, that have therapeutic potential as asthma drugs.

ABSTRACT: Two-dimensional (2D) correlation spectroscopy is a powerful analytical technique developed originally for IR spectroscopy to probe submolecular level dynamics and interactions of a system under some external physical perturbation. In 2D IR, a spectrum defined by two independent wavenumber axes is generated by applying a correlation analysis to a series of systematically varying spectra. Because of the specificity of absorption bands to chemical groups, perturbation-induced variations of spectral signals contain surprisingly rich information about the unique behavior of individual submolecular moieties comprising the system. The basic concept of displaying the distribution of correlation intensities on a two-dimensional spectral plane can also be readily extended to the analysis of data obtained as functions of many different types of physical variables, e.g., time, temperature, composition, pressure, location, sample type, and so on. Such spectra may be obtained not only for IR but also for many other branches of spectroscopic studies, including Raman, NIR, X-ray, UV-visible, or NMR spectroscopy. Some of the notable features of 2D correlation spectra are: simplification of complex spectra consisting of many overlapped peaks, enhancement of spectral resolution by spreading peaks over the second dimension, establishment of unambiguous band assignment through correlation of bands selectively coupled by various interaction mechanisms, and determination of the sequential order of events depicted by asynchronous changes in spectral intensities. In this presentation, a brief introduction of the technique is provided. An efficient and simple computational method for constructing 2D correlation spectra from any reasonable set of spectral data is given. And basic properties and a method of interpreting 2D spectra will be explained. To demonstrate the potential utility and versitilty of this technique, various illustrative examples of 2D correlation spectra will be presented for synthetic and biological materials, including the bio-based biodegradable plastics, which is an interesting novel class of polymers made by bacteria with an attractive set of properties.

ABSTRACT: Biopolymers exhibit a robust relationship between the sequence of their monomer units, their well-defined three-dimensional structures, and their diverse functions. We seek to recapitulate this sequence-structure-function relationship in a synthetic polymer system. We have explored the folding and functional attributes of peptoid oligomers, which are composed of specific sequences of highly diverse N-substituted glycine monomers. Despite the inability of the peptoid backbone to form hydrogen bond networks, we have identified peptoid sequences that can form mimics of protein secondary structures, such as helices and hairpin turns. Recent studies have now begun to identify peptoids with valuable functions, including selective catalysis and antimicrobial activity. Peptoid oligomers can also be used as a scaffold for precise multivalent display, enabling modulation of nuclear hormone receptor activity for potential therapeutic applications. The future prospects for computational design of complex peptoid folds will be evaluated.

Thursday, April 19, 2012

DR. STEPHEN MARTIN

University of Texas - Austin

“Correlating Structure and Energetics in Protein-Ligand Interactions: Paradigms and Paradoxes”

ABSTRACT: We are interested in exploring how introducing specific structural modifications into peptides and other small molecules effects thermodynamics in protein-ligand interactions. This is arguably one of the most challenging problems in contemporary molecular recognition in biological systems and in the applied field of drug discovery. One common design strategy for increasing ligand binding affinity is to introduce conformational constraints in order to preorganize a flexible molecule in the conformation that corresponds to its biologically active conformation. The fundamental premise for this approach is the general belief that there will be a smaller entropic penalty on binding for the constrained molecule relative to its flexible counterpart that will lead to increased affinity, provided the two ligands interact in the same way with water and the protein. This caveat is applied with the view that binding enthalpies for the two ligands will be approximately the same. Another successful tactic for improving ligand binding affinity is to increase its hydrophobicity by introducing aliphatic and/or aromatic substituents. This design rationale owes its origin to the common interpretation of the hydrophobic effect, which suggests that enhanced potency will accompany the entropic gain associated with desolvation of nonpolar surfaces. However, it is now increasingly apparent that prevailing paradigms regarding the energetic consequences associated with making specific changes in ligand structure upon the resultant binding affinities are not necessarily valid. Recent results from our laboratories relevant to how ligand preorganization and nonpolar surface effect binding enthalpies and entropies in protein-ligand interactions will be presented.

ABSTRACT: This lecture deals with ambient ionization mass spectrometry - the chemical analysis of complex samples performed directly in air on untreated samples. The prototype method, DESI, uses charged solvent droplets to characterize materials including biological fluids and tissue.

The mechanism of DESI has been elucidated using data from laser tomography and simulations of fluid flow. In situ chemical reactions can be performed in concert with ionization on the milli-second time scale because rates of reactions in microdroplets are greatly accelerated compared to bulk solution. Calculations which address the underlying reasons for rate acceleration are reported and the contributions of molecular entanglement to rate acceleration are distinguished from those arising from decreased energy requirements (changes in the reaction potential energy surfaces) associated with desolvation.

The use of DESI in chemical imaging, especially to distinguish disease states in tissue, is described. Applications to renal, prostate, testicular, and bladder cancer use lipid profiles. Special attention is given to distinguishing the type and stage of brain cancers and to methodology that can provide intrasurgical diagnostic information. These applications require data compilations and automated multivariate data reduction methods to allow rapid disease state characterization.

A related ambient ionization method, paper spray, is shown to allow quantitative levels of therapeutic drugs to be determined in whole blood in a point-of-care fashion.

Also described are new developments in miniature mass spectrometers that employ this ionization method. Progress in interfacing ambient ionization sources to miniature mass spectrometers is described. .

The support of this work by NSF, DOE, the James S. McDonnell Foundation and the Alfred Mann Foundation at Purdue and collaborations with Prof. Zheng Ouyang and Dr. Nathalie Agar are gratefully acknowledged.

Thursday, April 5,
2012

DR. ELON ISON

North Carolina State University

“Development of Re and Ir Complexes as Catalysts for Oxygen Atom Transfer and C-H Activation/ Functionalization”

ABSTRACT: The development of homogeneous catalysts for the efficient utilization of our chemical feedstocks will be described. Specifically, we will discuss our efforts at synthesizing novel oxorhenium catalysts for the conversion of syngas to high value chemicals. The discovery of a new mechanism for the activation of CO by transition metal oxos will be discussed (Scheme 1).

In addition we will discuss our efforts at developing new catalysts for the catalytic functionalization of C-H bonds. This work is in conjunction with the Center for Enabling New Technologies through Catalysis (CENTC). We will describe new insights into the activation of C-H bonds by Cp*Ir(NHC) complexes (NHC = N-Heterocyclic carbene) as a function of the solvent used for H/D exchange reactions of benzene and a variety of deuterium sources. We will also describe a new catalytic method for the functionalization of benzoic acids to produce benzo[c]chromen-6-ones.

Thursday, March 29, 2012

DR. AMY BARRIOS

University of Utah

“ Chemical Probes Put Tyrosine Phosphatase Activity in the Spotlight”

ABSTRACT: The protein tyrosine phosphatases (PTPs) are among the most intriguing enzymes in the human genome. They play critical and unique roles in cellular signaling pathways, recognize a diverse set of tyrosine phosphorylated protein substrates and are tightly regulated on multiple levels. Our laboratory has been working to develop the “molecular toolkit” necessary for understanding the activity and regulation of PTPs. Fluorogenic probes useful in visualizing enzyme activity have been developed and used in high-throughput screens for novel PTP inhibitors. These inhibitors serve as chemical probes for PTP activity in cells and in vivo, providing “chemical knock-outs” of the lymphoid tyrosine phosphatase, a PTP that is important in the immune response. Notably, our lead compound shows efficacy in reducing anaphylaxis in mice.

Thursday, March 22, 2012

DR. CHERIE KAGAN

University of Pennsylvania

“ The Role of Surface Ligands In Electronic Charge Transport In Semiconductor Nanocrystal Arrays”

ABSTRACT: The long, insulating ligands commonly used in the synthesis of colloidal semiconductor nanocrystals (NCs) inhibit strong interparticle coupling and charge transport once NCs are assembled in the solid state into NC arrays. We introduce ammonium thiocyanate (NH4SCN) to exchange the long, insulating ligands commonly used in the synthesis of colloidal semiconductor NCs. NCs may be exchanged with the new ligand in solution to form dispersions from which NC arrays are deposited or NC arrays with the long, insulating ligands may be exchanged in the solid state with the new ligands. The new compact ligands enhance interparticle coupling and charge transport in thin film, NC arrays as seen by red-shifts in the optical absorption and concomitant increases in carrier mobilities. Thiocyanate-capped CdSe thin film, NC arrays form sensitive photodetectors and n-type field-effect transistors with electron mobilities of ~25 cm2/Vs and current modulation of >106, while preserving NC quantum confinement. Temperature-dependent transport measurements reveal band-like transport in NC arrays, overcoming carrier hopping that has typified transport in NC arrays until recently. The non-caustic, chemically benign nature of the ammonium thiocyanate treatment enables the fabrication of NC thin film devices and circuits on flexible plastics.

Thursday, March 8, 2012

DR. GREGORY BERAN

University of California (Riverside)

“Predicting Molecular Crystal Properties with Quantum Chemistry”

ABSTRACT: Molecular crystal structure affects the bioavailability of pharmaceuticals, the charge carrier efficiency of organic semiconductors, the products of solid-state reactions, and the explosive performance of energetic materials. Because different packing arrangements, or polymorphs, are often very close in energy, predicting molecular crystal properties from first principles is extremely difficult. We have developed a new, fragment-based quantum/classical hybrid model that makes it possible to apply high-level electronic structure methods to molecular crystal structure prediction. This model treats intramolecular effects and short-range pairwise intermolecular interactions quantum mechanically, while longer-range and many-body interactions are approximated classically. We will demonstrate that this model makes it possible to predict small-molecule crystal lattice energies essentially to within experimental accuracy. Then we will examine its performance in more interesting polymorphic crystals, such as aspirin.

ABSTRACT: Amination based on metal-catalyzed nitrene C–H insertion represents a powerful approach for the direct transformation of ubiquitous C–H bonds into valuable amine functionalities while offering potential control of various types of selectivities. Departing from the widely-used Rh(II)2 and other closed-shell catalysts, we have been focused our efforts in developing open-shell cobalt(II) porphyrin complexes ([Co(Por)]) as metalloradical catalysts for C–H amination. The [Co(Por)]-based metalloradical amination is unusual as it can effectively activate different azides as the nitrene sources under neutral and nonoxidative conditions, with the generation of nitrogen gas as the only by-product. Because it obviates the need for terminal oxidants and other additives, the [Co(Por)]/azide catalytic system has a high degree of functional group tolerance in addition to its operational simplicity. As demonstrated with several intramolecular processes, the Co(II)-catalyzed reactions possess uncommon capability for efficient amination of strong primary C–H bonds and exhibit remarkable chemoselectivity toward allylic C–H amination over competitive C=C aziridination. These and other unique reactivities and selectivities are attributed to the underlying radical mechanism of Co(II)-based metalloradical catalysis.

ABSTRACT: Important chemistry often occurs at interfaces. In dye sensitized solar cells, charge injection occurs at the molecular interface. The cytotoxicity of antibiotics is caused by structures at the membrane interface. While important, molecular structures are very difficult to study at interfaces.

In this talk, I will present our work utilizing advanced multidimensional spectroscopy to study interfaces in biological and materials systems.

Thursday, February 9, 2012

DR. KRZYSZTOF MATYJASZEWSKI

Carnegie Mellon University

“From New Synthetic Procedures for ATRP to New Materials”

ABSTRACT: Copper-based ATRP (atom transfer radical polymerization) catalytic systems with polydentate nitrogen-based ligands is among most efficient controlled/living radical polymerization systems. Recently, by applying new initiating/catalytic systems, Cu level in ATRP was reduced to a few ppm. Various reducing agents, including metals, organometallic species, sugars, amines, phenols, monomers ligands, radical initiators or electrical current have been successfully applied. Similar control can be achieved with ppm of Fe-based catalysts. ATRP of acrylates, methacrylates, styrenes, acrylamides, acrylonitrile and many other vinyl monomers provides polymers with molecular weights in a large range 200<Mn<20,000,000 and with low dispersities. Polymers can be formed quantitatively in bulk, in solution and in dispersed media. Water can serve both as solvent for many water soluble polymers and also as medium for microemulsion, miniemulsion, dispersion and suspension polymerization. Block, graft, star, hyperbranched, gradient and periodic copolymers, molecular brushes and various hybrid materials as well as bioconjugates have been prepared. The (co)polymers made by ATRP have many potential applications as components of advanced materials such as coatings, elastomers, adhesives, surfactants, dispersants, lubricants, additives, but also as specialty materials in biomedical and electronic areas and will affect the market of ~$20 billion/year. Macromolecular engineering comprising design, synthesis, characterization and applications of nanostructured multicomponent polymeric materials prepared via ATRP will be presented.

ABSTRACT: We have launched three major research efforts to use quantum mechanics techniques to search for robust, efficient, and inexpensive materials for solid oxide fuel cells (SOFCs) that convert fuels to electricity, photovoltaics (PVs) that convert sunlight to electricity, and photo-catalytic electrodes (PCEs) that convert sunlight, carbon dioxide, and water into fuels. Various observables that are key metrics for determining the utility of a given material can be accurately calculated from quantum mechanics; we will discuss our theoretical schemes for each observable and how we validate our approach. In our SOFC research, we are focusing on cathode optimization, often considered the limiting factor in reducing the high operating temperatures of current SOFCs. Porous electrodes can be readily synthesized for SOFCs such that gas transport is facile. If oxide ion diffusion and electron transport could be enhanced, along with rapid dissociative adsorption of dioxygen on the cathode surface, lower temperatures could be used, which would facilitate wider deployment. In the solar energy conversion arena, the cost-efficiency tradeoff for PV materials motivates a look at new options and despite periodic media reports to the contrary, no efficient PCEs are available yet. I will discuss why it is so difficult to find effective PCE materials; in particular I will enumerate the very significant constraints beyond those on PVs that they must satisfy to achieve high efficiency. Limiting oneself to abundant elements further constrains the design space. As a result, we are focusing primarily on first row transition metal oxide materials. Key properties of conventional and novel materials, along with some new design principles, will be discussed. The work is revealing which dopants or mixed oxides are likely to provide the most efficient energy conversion materials.

Thursday, February 2, 2012

DR. VERN L. SCHRAMM

Albert Einstein College of Medicine (Bronx)

“
TRANSITION STATES AND DYNAMICS IN ENZYMATIC CATALYSIS”

ABSTRACT: Faithful mimics of enzymatic transition state structures are powerful inhibitors of enzymes. Details of enzymatic transition states comes from a combination of experimental kinetic isotope effects and quantum chemistry. The resulting information permits chemical synthesis of transition state analogues. These typically bind millions of times tighter to enzymes than substrates. Several of our designed analogues are in clinical trials. Transition state analogues in complex with enzymes provide answers to transition state lifetimes, motion at the transition state, and roles of slow and fast dynamic motion to enzyme chemistry.

Thursday, December 1, 2011

DR. DANIEL SEIDEL

Rutgers University (Piscataway)

“Redox Neutral Reaction Calcades and New Concepts in Asymmetric Catalysis”

ABSTRACT: Our recent efforts in developing new concepts for asymmetric organocatalysis will be presented. The lecture will also cover the development of redox neutral reactions that lead to mild C-H bond functionalization and rapid buildup of molecular complexity..

Thursday, October 27, 2011

DR. GARY BRUDVIG

Yale University

"Water Oxidation Chemistry of Photosystem II and Artificial Systems”

ABSTRACT: Photosystem II (PSII) uses light energy to split water into protons, electrons and O2. In this reaction, Nature has solved the difficult chemical problem of efficient four‑electron oxidation of water to yield O2 without significant side reactions. In order to use Nature’s solution for the design of materials that split water for solar fuel production, it is important to understand the mechanism of the reaction. X‑ray crystal structures of cyanobacterial PSII provide information on the structure of the Mn and Ca ions, the redox-active tyrosine called YZ, and the surrounding amino acids that comprise the O2‑evolving complex (OEC). The structure of the OEC and the mechanism of water oxidation by PSII will be discussed in the light of biophysical and computational studies, inorganic chemistry and recent X-ray crystallographic information. These insights on the natural photosynthetic system are being applied to develop bioinspired materials for photochemical water oxidation and fuel production. Our progress toward the development of materials for artificial photosynthesis will be discussed.

Thursday, November 10, 2011

DR. LOUIS BRUS

Columbia University

"Electron Correlation In Carbon Nanotubes and Graphene”

ABSTRACT:
We explore the fundamental nature and dynamics of excited electronic states in graphitic carbon materials. In semiconducting carbon nanotubes, near-infrared two photon luminescence excitation spectra quantitatively reveal very-strongly-bound exciton excited states. Electron-electron interactions are compared among CdSe nanocrystals, graphene, and carbon nanotubes. The independent contributions of screening and dimensionality are analyzed. Electronic and vibrational degrees of freedom are significantly coupled in graphene. The metallic versus molecular nature of single sheet graphene is strongly affected by charge transfer doping by adsorbed molecular species. Asymmetric doping in bilayer graphene can open a band gap, as revealed by the Raman spectra. Optical absorption bleaching and Raman Fano lineshapes are observed in few layer graphenes very highly doped by adsorbed alkalis.

Thursday, November 3, 2011

DR. RODERICK KUNZ

MIT Lincoln Laboratory

“Laser-Based Remote Detection of
Trace Explosives”

ABSTRACT: The development of a technique with the ability to detect trace quantities of explosives at a distance is of great interest since the detection of such residues can be an indicator for attempts at concealed assembly or transport of explosive materials and devices. In order to be of practical use, the desired detection technique must be rapid and effective from a distance. Measures of effectiveness include high sensitivity to traces of the target compounds and the ability to detect a broad range of explosive materials. Such measures also include low susceptibility to false alarms, a requirement that is often at odds with that of high sensitivity. Several laser-based remote detection methods have been under investigation, including those relying on Raman scattering and laser-induced breakdown spectroscopy.
This seminar describes an alternative approach, which involves ultraviolet photodissociation of condensed-phase material, followed by laser-induced fluorescence of the photofragment nitric oxide. A significant fraction of the photofragment from the dissociation of organo-nitrate explosives is formed in vibrationally excited states. This circumstance is conducive to generating laser-induced fluorescence at wavelengths shorter than the excitation wavelength, thereby significantly reducing the probability of false alarms. Laboratory demonstrations with single laser pulses of several nanoseconds' duration indeed exhibit a high detection efficiency with low false-alarm rates. Further development of this method will require a combination of phenomenological surveys, photochemical studies, and laser engineering.

Thursday, October 13, 2011

DR. FLAVIO MARAN

University of Padova - Italy

"Superefficient Electron Transfer Through 310-Helical Peptides”

ABSTRACT:
Electron transfer (ET) reactions are of fundamental importance in a variety of areas of chemistry and biology. Our current understanding of the rate and mechanisms of long-range ETs between an electron donor and an electron acceptor relies on careful experimental and theoretical studies of DNA, protein, and peptide systems. Since peptides are key elements of long-range ETs in proteins and can play a considerable role in biosensing, one fundamental question is: among possible peptides, which are likely to provide particularly efficient ET bridge systems? We synthesized a series of thiolated oligopeptides of a-aminoisobutyric acid and used them to prepare self-assembled monolayers (SAMs) on Au electrodes. These peptides form 310-helices and were devised to possess from zero to eight C=O···H-N intramolecular hydrogen bonds. The peptide-SAM electrodes were used to determine the standard heterogeneous rate constant for the reduction of Ru(NH3)6Cl3 in 0.5 M KCl aqueous solution. The results show that as the peptide length increases the ET rate initially decreases but then, for sufficiently long peptides, displays a remarkably shallow dependence on distance. The possible ET mechanisms are discussed.

Thursday, September 29, 2011

DR. GEORGE A. PETERSSON

Wesleyan University

“ Simple Models”

ABSTRACT: Simple physical models often provide innsight into problems that are too complex to allow a closed form solution. For example, the particle in a box problem provides a simple model for polyene spectra, gives and intuitive understanding of the general structure of eigenvalues of the time independent Schrodinger equation, and provides a qualitative understanding of the basis set convergence of configuration interaction calculations. A spherical atom model (SAM) for dispersion combined with density functional theory predicts the equilibrium bond lengths of the rare-gas dimmers to within ±0.02Å rms error.This new APF-D functional predicts potential energy surfaces of hydrocarbons and relative conformational energies of organic molecules with an accuracy comparable to CCSD(T)/aug-cc-pVTZ calculations.

“Natural Products: The Last Hurrah or Ready for the 21st Century in Drug Discovery?”

ABSTRACT:Many people have written off natural products as a source of drug leads in the last few decades. However, analyses of the “sources of drugs” that have been approved for all diseases, world-wide over the last three decades have consistently demonstrated that natural products, slight modifications or spatial mimics are still “alive and well."

This presentation will cover these analyses and then proceed to demonstrate how, in roughly the same time frame as the advent (and “demise?”) of classical combinatorial chemistry, its practitioners have been called back, frequently against their will, to produce focused libraries of molecules that resemble if not slavishly imitate, natural product structures as leads to drugs.

ABSTRACT:
The 21st century is witnessing a revolution in the area of electronics and photonics. Conventional semiconductor technology is being challenged by potentially inexpensive, flexible, large-area and light-weight organic devices. The design and development of electro- and photo-active molecular and polymeric materials with the desired chemical, physical, electronic and optical properties is critical in achieving high efficiency and stability in these devices. Different approaches taken for tuning the electronic structures of fluorescent, charge carrier transporting, and light-harvesting materials through molecular and interface engineering will be presented. Tuning the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels of a guest relative to a host molecules or an electron donor relative to an electron acceptor is essential for several device applications. For instance, designing guest and host molecules with the proper HOMO-LUMO energy gaps for the active emissive layer of an organic light-emitting diode is critical for efficient energy transfer from host to guest molecules and/or direct electron-hole (e--h+) recombination on the emitting guest molecules. Tailoring the organic/ metal interface through tuning of the HOMO and LUMO energy levels of the organic semiconductor relative to the work functions of the anode and cathode is necessary for good energy level alignment and efficient charge injection. Maximizing the separation between the HOMO energy level of an electron donor relative to that of the LUMO of an electron acceptor is necessary for efficient e--h+ separation in an organic solar cell, and will lead to a large built-in chemical potential and a high open circuit voltage. A review will be given on how these concepts are put together to develop electro- and photo-active materials, and engineer interfaces for efficient conversion of electrical energy into light and solar energy into electricity.

ABSTRACT: Although characterization of protein secondary structures at interfaces is important in biological and bioengineering sciences, it remains technically challenging. Here, we introduce a concept of using chiral vibrational optical markers provided by sum frequency generation (SFG) spectroscopy to identify protein secondary structures at interfaces. We observe characteristic chiral N-H stretch and amide I vibrational signatures unique to random-coil, alpha-helix and beta-sheet at interfaces. Using these vibrational signatures as optical markers, we monitor in situ and in real time the aggregation of an amyloid protein from random coil to alpha-helix and then beta-sheet at a lipid-water interface. Our findings demonstrate that chiral SFG can be a complementary method in characterizing interfacial protein structures for solving problems that may not be attacked by conventional methods.

ABSTRACT: The electrochemically synthesized materials and structures are often enabling resources in high-tech enterprise. The sub-100nm structures are produced routinely using the electrodisposition, anodization and electropolishing as the standard processing operations in magnetic recoding, microprocessors and MEMS/NEMS technologies. In some instances, the electrochemical material synthesis and nanostructure fabrication is the only approach to deliver desired catalysts, alloys, conductive polymers, nanoporous metals, etc...

In this talk, the examples of the electrochemical synthesis of materials and nanostructures are presented. In the first part, the optimum design and synthesis of Pt catalyst monolayer (ML) on Au(III) is demonstrated using surface limited red-ox replacement reaction (SLRR). The morphology of the most active catalyst ML is identified and discussed in relation to the size dependent strain effect on d-band center position of Pt catalyst ML. The experiemntal results are compared with predictions of DFT calculations and the observed trends were found in qualitative agreement. The new synthesis route for catalyst ML fabrication using SLRR guided by molecular templates is presented and discussed as well. The second part of the talk reveals the science and art of additives in electrodeposition process of magnetic films. The relation between concentration of organic additves in electrodisposition process of magnetic fields. The relation between concentration of organic additives in the solution and their incorporation into magnetic alloys is described. The dependence of magnetic, corrosion and mechanical properties of electrodeposited CoFe alloys on additive concentration in the solution is quantified shining a new light to the understanding and appreciation of the organic adsorption phenomenon during electrodisposition process.

Friday, April 15, 2011

DR. LILLIAN T. CHONG

University of Pittsburgh

"Molecular Simulations of Protein Binding and Switching"

ABSTRACT: A major challenge in the field of biomolecular simulations is to access the long-timescale dynamics of biologically relevant protein motions such as the relative motios of protein domains and allosteric transitions. My group uses a variety of approaches for providing detailed views of such motions that might aid the design of molecular sensors or therapeutics. In this talk, I will present recent applications to the simulation of large-scale conformational changes in bi-functional, two-domain protein switches, molecular association kinetics, and how nature might correct for "mistakes" in binding geometry for a model protein-peptide complex.

Thursday, April 14, 2011

DR. PATRICK HOLLAND

University of Rochester

"Understanding the Mechanism of Nitrogen Fixation Using Low-Coordinate Iron Complexes"

ABSTRACT: Iron plays a central role in the large-scale reduction of dinitrogen to ammonia by nature (nitrogenase enzymes) and by industry (Haber-Bosch process). Despite intense research, the catalytic mechanisms and the role of iron have remained a mystery. This seminar will describe how advances in the synthesis of low-coordinate iron coordination compounds have led to iron complexes with weakened nitrogen-nitrogen bonds. Manipulation of the supporting ligands has now enabled the first N-N bond cleavage and ammonia formation using iron complexes. The results help chemists to identify potential active sites of the catalytic dinitrogen reduction reactions, through characterization of elementary steps in the conversion of dinitrogen to ammonia.

ABSTRACT: My Research group's focus is twofold - in one direction our efforts focus on constructing small-molecule structural and functional analogs of metalloenzyme active sites, and in the other direction we take inspiration from these enzyme active sites to synthesize transition metal complexes that exhibit some of the key functions of these systems, including catalytic behavior and bond-making/bond-breaking steps. One part of this talk will focus on our recent work involving the synthesis of mononuclear, non-heme iron model complexes of the enzymes cysteine dioxygenase (CDO) and super oxide reductase (SOR). We have recently reported the synthesis of the first structural and fuctional models of CDO. These Fe(II)/Fe(III) complexes are derived from ligands designed to include the mixed nitrogen/sulfur donation found in the enzymes. Low-temperature methods are used to trap Fe-(III)-OOR intermediated of relevance to SOR. Some of these Fe(II) complexes activate O2 to give selective sulfur oxygenation, mimicking the CDO enzyme. A second part of this talk will focus on work with a porphyrinoid system that we call corrolazines, which are designed to stabilize high oxidation state metal complexes. The reactivity of these complexes in both oxygen-atom-transfer and proton-coupled electron-transfer (PCET) chemistry will be discussed from a synthetic, mechanistic, and spectroscopic view. For example, the C-H activation capabilities of a remarkably stable, high-valent manganese(V)-oxo corrolazine is described, including some dramatic rate enhancement effects via attachment of axial ligands.

Thursday, March 24, 2011

DR. DENNIS C. LIOTTA

Emory University

"New Therapies Inspired By Nature For Treating Cancer and Inflammation"

ABSTRACT: The combined efforts of chemists, pharmacologists and biochemists at Emory have successfully resulted in the development of novel and selective preclinical and clinical agents of biomedical interest. I will breifly describe two projects involving collaboration with Emory University School of Medicine faculty. In the first project we have prepared a variety of sphingolipid analogs that function as anticancer agents by hitting multiple targets synergistically, thereby reducing the liklihood of resistance. In the second project we have prepared a variety of analogs of the natural product, triptolide, that exhibit excellent anti-inflammatory properties. In both of these projects we challenge traditional dogma regarding the molecular and pharmacologic properties desirable for drug candidates.

Wednesday, March 23, 2011

DR. ANGUS BAIN

Universal College of London

"Time Resolved Fluorescence & Stimulated Emission Depletion"

Monday, March 21, 2011

DR. ABRAHAM CLEARFIELD

Texas A& M University

"Layered Nanoparticles For Surface Chemistry and Drug Delivery"

Friday, March 18, 2011

DR. PARAJMIT ARORA

New York University

"A Systematic Approach To Targeting Protein Interfaces"

ABSTRACT: Proteins often utilize small folded domains for recognition of other biomolecules. The basic hypothesis guiding our research is that by mimicking these folded domains we can modulate the function of a particular protein with metabolically stable synthetic molecules. Our strategy for developing structured oligomers and their potential in targeting "undruggable" protein-protein interactions will be discussed.

Thursday, March 17, 2011

DR. LAWRENCE J. WILLIAMS

Rutgers State University

“Integrated Routing: An Approach To The Synthesis Of 'N' Natural Products As 'N' Approaches Infinity”

ABSTRACT:Distinctly new methods of chemical synthesis that are applicable to complex molecule preparation represent shifts in planning syntheses. The methodology field is highly dynamic and, perforce, so is synthetic planning. However, strategic analysis (i.e. the way in which we conceptualize the problem of synthesis and the guiding principles of synthetic planning) may not appear to have changed significantly since its formalization several decades ago. Nevertheless, it has. In the search for bioactive compounds via chemical synthesis single target strategic analysis is not optimal for multitarget synthesis. This is especially true as the number of targets becomes very large and as the targets become increasingly dissimilar. This lecture will discuss synthetic analysis of complex molecules in this context and will illustrate integrated routing strategies with progress towards the synthesis of structurally diverse natural products and their edited variants.